Nutrient chapter

GSH

Reducing cosubstrate in glutathione peroxidase assays.

188 recorded mechanisms · 24 availability situations · 24 preserved sources. Draft and verified records are labeled separately.

Read recorded mechanisms Open recursive mind map

The mechanisms

What the sources say this nutrient does, one relationship at a time. Plain wording comes first; the technical statement follows.

Human GSS crystallized with two magnesium ions, ADP, glutathione and sulfate.
Mg2+ → Human glutathione synthetase / GSS source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/10369661.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ccdd02e451ba6a6d432012c382911ff7fac556e99f9e8d60ce9f3dc94baf9941", "start_char": 0, "end_char": 1327, "text_sha256": "ccdd02e451ba6a6d432012c382911ff7fac556e99f9e8d60ce9f3dc94baf9941"}
experimental_model
Crystal structure and disease-variant mapping
exposure
ADP/GSH/sulfate-bound structure
limitations
Two Mg ions observed; structure is not a dietary-magnesium depletion experiment. The main synthesis reaction is reused from its existing claim.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human enzyme
plain_language
The synthesis enzyme has a metal-containing nucleotide-binding environment.
primary_references
[glutathione-p10369661] Molecular basis of glutathione synthetase deficiency and a rare gene permutation event. (1999). https://pubmed.ncbi.nlm.nih.gov/10369661/ DOI: 10.1093/emboj/18.12.3204
tissue_or_cell_type
Purified GSS
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 333–344
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystal structure and disease-variant mapping · source_derived_draft · unverified_draft
### glutathione-gss-magnesium Human GSS crystallized with two magnesium ions, ADP, glutathione and sulfate. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The synthesis enzyme has a metal-containing nucleotide-binding environment. organism: Human enzyme tissue_or_cell_type: Purified GSS experimental_model: Crystal structure and disease-variant mapping limitations: Two Mg ions observed; structure is not a dietary-magnesium depletion experiment. The main synthesis reaction is reused from its existing claim. exposure: ADP/GSH/sulfate-bound structure evidence_span: {"source_cache": "artifacts/glutathione-research/10369661.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ccdd02e451ba6a6d432012c382911ff7fac556e99f9e8d60ce9f3dc94baf9941", "start_char": 0, "end_char": 1327, "text_sha256": "ccdd02e451ba6a6d432012c382911ff7fac556e99f9e8d60ce9f3dc94baf9941"} [glutathione-p10369661] Molecular basis of glutathione synthetase deficiency and a rare gene permutation event. (1999). https://pubmed.ncbi.nlm.nih.gov/10369661/ DOI: 10.1093/emboj/18.12.3204
Complete structured claim and evidence
SLC25A39 loss reduced mitochondrial GSH import.
Human mitochondrial glutathione carrier SLC25A39 → Mammalian mitochondrial glutathione import source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/34707288.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5", "start_char": 0, "end_char": 1450, "text_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5"}
experimental_model
Organelle metabolomics, genetics and targeted synthesis rescue
exposure
SLC25A39 loss, A39/A40 double loss and targeted GshF
limitations
Mitochondrial versus total-cell pools differ; engineered synthesis rescue is not oral supplementation.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Mammalian cells; separate mouse erythropoiesis experiments
plain_language
Making glutathione is not enough if it cannot enter this compartment.
primary_references
[glutathione-p34707288] SLC25A39 is necessary for mitochondrial glutathione import in mammalian cells. (2021). https://pubmed.ncbi.nlm.nih.gov/34707288/ DOI: 10.1038/s41586-021-04025-w
tissue_or_cell_type
Mitochondria
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 450–461
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Organelle metabolomics, genetics and targeted synthesis rescue · source_derived_draft · unverified_draft
### glutathione-a39-import SLC25A39 loss reduced mitochondrial GSH import. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Making glutathione is not enough if it cannot enter this compartment. organism: Mammalian cells; separate mouse erythropoiesis experiments tissue_or_cell_type: Mitochondria experimental_model: Organelle metabolomics, genetics and targeted synthesis rescue limitations: Mitochondrial versus total-cell pools differ; engineered synthesis rescue is not oral supplementation. exposure: SLC25A39 loss, A39/A40 double loss and targeted GshF evidence_span: {"source_cache": "artifacts/glutathione-research/34707288.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5", "start_char": 0, "end_char": 1450, "text_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5"} [glutathione-p34707288] SLC25A39 is necessary for mitochondrial glutathione import in mammalian cells. (2021). https://pubmed.ncbi.nlm.nih.gov/34707288/ DOI: 10.1038/s41586-021-04025-w
Complete structured claim and evidence
Whole-cell GSH levels were not reduced by SLC25A39 loss.
SLC25A39-knockout mammalian cells → Cellular reduced-glutathione pool source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/glutathione-research/34707288.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5", "start_char": 0, "end_char": 1450, "text_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5"}
experimental_model
Organelle metabolomics, genetics and targeted synthesis rescue
exposure
SLC25A39 loss, A39/A40 double loss and targeted GshF
limitations
Mitochondrial versus total-cell pools differ; engineered synthesis rescue is not oral supplementation.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Mammalian cells; separate mouse erythropoiesis experiments
plain_language
A normal total-cell result could conceal a mitochondrial shortage.
primary_references
[glutathione-p34707288] SLC25A39 is necessary for mitochondrial glutathione import in mammalian cells. (2021). https://pubmed.ncbi.nlm.nih.gov/34707288/ DOI: 10.1038/s41586-021-04025-w
tissue_or_cell_type
Mitochondria
trigger_kind
machinery_impairment Imported condition classification; unverified.
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 476–487
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Organelle metabolomics, genetics and targeted synthesis rescue · source_derived_draft · unverified_draft
### glutathione-a39-cellular-null Whole-cell GSH levels were not reduced by SLC25A39 loss. Condition category: machinery_impairment nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: A normal total-cell result could conceal a mitochondrial shortage. organism: Mammalian cells; separate mouse erythropoiesis experiments tissue_or_cell_type: Mitochondria experimental_model: Organelle metabolomics, genetics and targeted synthesis rescue limitations: Mitochondrial versus total-cell pools differ; engineered synthesis rescue is not oral supplementation. exposure: SLC25A39 loss, A39/A40 double loss and targeted GshF evidence_span: {"source_cache": "artifacts/glutathione-research/34707288.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5", "start_char": 0, "end_char": 1450, "text_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5"} [glutathione-p34707288] SLC25A39 is necessary for mitochondrial glutathione import in mammalian cells. (2021). https://pubmed.ncbi.nlm.nih.gov/34707288/ DOI: 10.1038/s41586-021-04025-w
Complete structured claim and evidence
Human G6PD uses glucose-6-phosphate and catalytic NADP+ to generate NADPH.
Glucose-6-phosphate dehydrogenase / G6PD → NADPH source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/35858355.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "02c2d0e880b17ab304fab0854064813ffec5fa9e647b978a083aa88fbf8a38f0", "start_char": 0, "end_char": 1328, "text_sha256": "02c2d0e880b17ab304fab0854064813ffec5fa9e647b978a083aa88fbf8a38f0"}
experimental_model
Cryo-EM and structural comparison
exposure
Ligand-free and NADP/G6P-bound states
limitations
Structural NADP and catalytic NADP are different sites; enzyme activity is not a niacin-treatment trial.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
The reducing power used in glutathione recycling has to be replenished.
primary_references
[glutathione-p35858355] Allosteric role of a structural NADP+ molecule in glucose-6-phosphate dehydrogenase activity. (2022). https://pubmed.ncbi.nlm.nih.gov/35858355/ DOI: 10.1073/pnas.2119695119
tissue_or_cell_type
Purified wild-type G6PD and D200N
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 762–773
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM and structural comparison · source_derived_draft · unverified_draft
### glutathione-g6pd-nadph Human G6PD uses glucose-6-phosphate and catalytic NADP+ to generate NADPH. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The reducing power used in glutathione recycling has to be replenished. organism: Human tissue_or_cell_type: Purified wild-type G6PD and D200N experimental_model: Cryo-EM and structural comparison limitations: Structural NADP and catalytic NADP are different sites; enzyme activity is not a niacin-treatment trial. exposure: Ligand-free and NADP/G6P-bound states evidence_span: {"source_cache": "artifacts/glutathione-research/35858355.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "02c2d0e880b17ab304fab0854064813ffec5fa9e647b978a083aa88fbf8a38f0", "start_char": 0, "end_char": 1328, "text_sha256": "02c2d0e880b17ab304fab0854064813ffec5fa9e647b978a083aa88fbf8a38f0"} [glutathione-p35858355] Allosteric role of a structural NADP+ molecule in glucose-6-phosphate dehydrogenase activity. (2022). https://pubmed.ncbi.nlm.nih.gov/35858355/ DOI: 10.1073/pnas.2119695119
Complete structured claim and evidence
Each GLRX5-bound [2Fe-2S] cluster was ligated by two protein Cys67 thiols and two GSH cysteine thiols.
GSH → Human GLRX5 [2Fe-2S]-glutathione complex source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/21029046.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bc7e33127eee3685d1f90bff5a83334d68ac0ee3f73eeb67e4a9e189c5ba20b2", "start_char": 0, "end_char": 1468, "text_sha256": "bc7e33127eee3685d1f90bff5a83334d68ac0ee3f73eeb67e4a9e189c5ba20b2"}
experimental_model
Crystallography, solution oligomers and biochemical assays
exposure
Iron-sulfur/GSH complex and disulfide assays
limitations
The structural cluster complex is not a dietary-iron requirement or proof of supplement synergy.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human GLRX5
plain_language
Glutathione is part of the cluster-binding structure, not only an antioxidant.
primary_references
[glutathione-p21029046] The crystal structure of human GLRX5: iron-sulfur cluster co-ordination, tetrameric assembly and monomer activity. (2011). https://pubmed.ncbi.nlm.nih.gov/21029046/ DOI: 10.1042/bj20101286
tissue_or_cell_type
Purified holo and apo protein
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 788–799
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystallography, solution oligomers and biochemical assays · source_derived_draft · unverified_draft
### glutathione-glrx5-gsh-ligand Each GLRX5-bound [2Fe-2S] cluster was ligated by two protein Cys67 thiols and two GSH cysteine thiols. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione is part of the cluster-binding structure, not only an antioxidant. organism: Human GLRX5 tissue_or_cell_type: Purified holo and apo protein experimental_model: Crystallography, solution oligomers and biochemical assays limitations: The structural cluster complex is not a dietary-iron requirement or proof of supplement synergy. exposure: Iron-sulfur/GSH complex and disulfide assays evidence_span: {"source_cache": "artifacts/glutathione-research/21029046.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bc7e33127eee3685d1f90bff5a83334d68ac0ee3f73eeb67e4a9e189c5ba20b2", "start_char": 0, "end_char": 1468, "text_sha256": "bc7e33127eee3685d1f90bff5a83334d68ac0ee3f73eeb67e4a9e189c5ba20b2"} [glutathione-p21029046] The crystal structure of human GLRX5: iron-sulfur cluster co-ordination, tetrameric assembly and monomer activity. (2011). https://pubmed.ncbi.nlm.nih.gov/21029046/ DOI: 10.1042/bj20101286
Complete structured claim and evidence
Human hxCTb required 4F2hc for sodium-independent cystine/glutamate transport in oocytes.
SLC7A11 → Cystine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/11406111.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e7118afd8c6055ed926ee24dbb7a07538f676163d605115ae0d32d49fbef7fdc", "start_char": 0, "end_char": 1364, "text_sha256": "e7118afd8c6055ed926ee24dbb7a07538f676163d605115ae0d32d49fbef7fdc"}
experimental_model
Human xCT expression and oxidative-stress response
exposure
hxCTb with 4F2hc; diethyl maleate challenge
limitations
Sodium independence belongs to this transporter; other cysteine-entry routes differ.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human transporter; Xenopus expression host
plain_language
The precursor-entry route depends on two transporter subunits.
primary_references
[glutathione-p11406111] Human cystine/glutamate transporter: cDNA cloning and upregulation by oxidative stress in glioma cells. (2001). https://pubmed.ncbi.nlm.nih.gov/11406111/ DOI: 10.1016/s0005-2736(01)00338-8
tissue_or_cell_type
Oocyte membranes and human U87 glioma cells
transport_effect
depends The record names the cystine/glutamate exchange pair and the 4F2hc requirement, not which way cystine crossed.
transport_pool
the cytosol across the plasma membrane The record names the cystine/glutamate exchange pair and the 4F2hc requirement, not which way cystine crossed.
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 736–747
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human xCT expression and oxidative-stress response · source_derived_draft · unverified_draft
### glutathione-xct-cystine Human hxCTb required 4F2hc for sodium-independent cystine/glutamate transport in oocytes. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The precursor-entry route depends on two transporter subunits. organism: Human transporter; Xenopus expression host tissue_or_cell_type: Oocyte membranes and human U87 glioma cells experimental_model: Human xCT expression and oxidative-stress response limitations: Sodium independence belongs to this transporter; other cysteine-entry routes differ. exposure: hxCTb with 4F2hc; diethyl maleate challenge evidence_span: {"source_cache": "artifacts/glutathione-research/11406111.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e7118afd8c6055ed926ee24dbb7a07538f676163d605115ae0d32d49fbef7fdc", "start_char": 0, "end_char": 1364, "text_sha256": "e7118afd8c6055ed926ee24dbb7a07538f676163d605115ae0d32d49fbef7fdc"} [glutathione-p11406111] Human cystine/glutamate transporter: cDNA cloning and upregulation by oxidative stress in glioma cells. (2001). https://pubmed.ncbi.nlm.nih.gov/11406111/ DOI: 10.1016/s0005-2736(01)00338-8
Complete structured claim and evidence
CHAC1 overexpression depleted GSH in HEK293 cells; a catalytic mutation alleviated that depletion.
Human glutathione-specific gamma-glutamylcyclotransferase CHAC1 → Cellular reduced-glutathione pool source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/25931127.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a561d11e802b38659805fe90dcab499bf0f434dbe91fa5510cf1eb4efb3460b1", "start_char": 0, "end_char": 1504, "text_sha256": "a561d11e802b38659805fe90dcab499bf0f434dbe91fa5510cf1eb4efb3460b1"}
experimental_model
Human promoter reporters, binding assays and overexpression
exposure
ER stress, ATF4 and CHAC1 expression
limitations
Cell experiments; CHAC1 induction is not a dietary GSH-deficiency diagnosis.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
Low glutathione can reflect increased breakdown, not just poor supply.
primary_references
[glutathione-p25931127] Human CHAC1 Protein Degrades Glutathione, and mRNA Induction Is Regulated by the Transcription Factors ATF4 and ATF3 and a Bipartite ATF/CRE Regulatory Element. (2015). https://pubmed.ncbi.nlm.nih.gov/25931127/ DOI: 10.1074/jbc.m114.635144
tissue_or_cell_type
HEK293 and U2OS cells
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 580–591
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human promoter reporters, binding assays and overexpression · source_derived_draft · unverified_draft
### glutathione-chac1-gsh CHAC1 overexpression depleted GSH in HEK293 cells; a catalytic mutation alleviated that depletion. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low glutathione can reflect increased breakdown, not just poor supply. organism: Human tissue_or_cell_type: HEK293 and U2OS cells experimental_model: Human promoter reporters, binding assays and overexpression limitations: Cell experiments; CHAC1 induction is not a dietary GSH-deficiency diagnosis. exposure: ER stress, ATF4 and CHAC1 expression evidence_span: {"source_cache": "artifacts/glutathione-research/25931127.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a561d11e802b38659805fe90dcab499bf0f434dbe91fa5510cf1eb4efb3460b1", "start_char": 0, "end_char": 1504, "text_sha256": "a561d11e802b38659805fe90dcab499bf0f434dbe91fa5510cf1eb4efb3460b1"} [glutathione-p25931127] Human CHAC1 Protein Degrades Glutathione, and mRNA Induction Is Regulated by the Transcription Factors ATF4 and ATF3 and a Bipartite ATF/CRE Regulatory Element. (2015). https://pubmed.ncbi.nlm.nih.gov/25931127/ DOI: 10.1074/jbc.m114.635144
Complete structured claim and evidence
Eye, liver and pancreatic GSH were markedly lower in Ggt1-null mice.
Ggt1-null mice in the 1996 study → Eye, liver and pancreatic glutathione in Ggt1-null mice source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/glutathione-research/8755578.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "94d2520bc0124611c649d943ab9acd9cdf73cd3cb99d66640338a57bda6f6dfb", "start_char": 0, "end_char": 1159, "text_sha256": "94d2520bc0124611c649d943ab9acd9cdf73cd3cb99d66640338a57bda6f6dfb"}
experimental_model
Targeted GGT gene disruption and NAC rescue
exposure
Ggt1-null versus wild type; oral NAC
limitations
Severe genetic salvage defect; high extracellular GSH did not mean adequate tissue stores.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Mouse
plain_language
The direction of change depended on the measured compartment.
primary_references
[glutathione-p8755578] Growth retardation and cysteine deficiency in gamma-glutamyl transpeptidase-deficient mice. (1996). https://pubmed.ncbi.nlm.nih.gov/8755578/ DOI: 10.1073/pnas.93.15.7923
tissue_or_cell_type
Plasma, urine, eye, liver and pancreas
trigger_kind
machinery_impairment Imported condition classification; unverified.
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 697–708
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Targeted GGT gene disruption and NAC rescue · source_derived_draft · unverified_draft
### glutathione-ggt-tissue Eye, liver and pancreatic GSH were markedly lower in Ggt1-null mice. Condition category: machinery_impairment nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The direction of change depended on the measured compartment. organism: Mouse tissue_or_cell_type: Plasma, urine, eye, liver and pancreas experimental_model: Targeted GGT gene disruption and NAC rescue limitations: Severe genetic salvage defect; high extracellular GSH did not mean adequate tissue stores. exposure: Ggt1-null versus wild type; oral NAC evidence_span: {"source_cache": "artifacts/glutathione-research/8755578.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "94d2520bc0124611c649d943ab9acd9cdf73cd3cb99d66640338a57bda6f6dfb", "start_char": 0, "end_char": 1159, "text_sha256": "94d2520bc0124611c649d943ab9acd9cdf73cd3cb99d66640338a57bda6f6dfb"} [glutathione-p8755578] Growth retardation and cysteine deficiency in gamma-glutamyl transpeptidase-deficient mice. (1996). https://pubmed.ncbi.nlm.nih.gov/8755578/ DOI: 10.1073/pnas.93.15.7923
Complete structured claim and evidence
Oral GSH did not significantly change erythrocyte reduced, oxidized or ratio glutathione measures.
Oral reduced glutathione regimen in the 2011 trial → Erythrocyte reduced, oxidized and ratio glutathione measures in the 2011 trial source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/21875351.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d6f87d899397204e2bfb9a70e2262ccdd14364350668fbb50906662149fc4f69", "start_char": 0, "end_char": 2042, "text_sha256": "d6f87d899397204e2bfb9a70e2262ccdd14364350668fbb50906662149fc4f69"}
experimental_model
Randomized double-blind placebo-controlled trial
exposure
GSH 500 mg twice daily for four weeks
limitations
Trial-specific null results; not proof that every dose, duration or formulation is inactive.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
The tested supplement did not improve this measured endpoint.
primary_references
[glutathione-p21875351] Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers. (2011). https://pubmed.ncbi.nlm.nih.gov/21875351/ DOI: 10.1089/acm.2010.0716
tissue_or_cell_type
40 healthy adults; 39 completed
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1139–1150
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft
### glutathione-oral-2011-null Oral GSH did not significantly change erythrocyte reduced, oxidized or ratio glutathione measures. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The tested supplement did not improve this measured endpoint. organism: Human tissue_or_cell_type: 40 healthy adults; 39 completed experimental_model: Randomized double-blind placebo-controlled trial limitations: Trial-specific null results; not proof that every dose, duration or formulation is inactive. exposure: GSH 500 mg twice daily for four weeks evidence_span: {"source_cache": "artifacts/glutathione-research/21875351.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d6f87d899397204e2bfb9a70e2262ccdd14364350668fbb50906662149fc4f69", "start_char": 0, "end_char": 2042, "text_sha256": "d6f87d899397204e2bfb9a70e2262ccdd14364350668fbb50906662149fc4f69"} [glutathione-p21875351] Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers. (2011). https://pubmed.ncbi.nlm.nih.gov/21875351/ DOI: 10.1089/acm.2010.0716
Complete structured claim and evidence
At six months, high-dose erythrocyte GSH increased within the reported 30–35% range versus baseline.
Oral reduced glutathione regimens in the 2015 trial → Human erythrocyte glutathione concentration, study-defined assay pool source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/24791752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388", "start_char": 0, "end_char": 1596, "text_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388"}
experimental_model
Six-month randomized double-blind placebo-controlled trial
exposure
250 or 1000 mg/day oral GSH; one-month washout
limitations
Pool increases reported relative to baseline; NK comparison was versus placebo. Biomarkers do not prove fewer illnesses or longer life.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
The measured compartment increased in the longer trial.
primary_references
[glutathione-p24791752] Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. (2015). https://pubmed.ncbi.nlm.nih.gov/24791752/ DOI: 10.1007/s00394-014-0706-z
tissue_or_cell_type
54 nonsmoking adults; immune subset
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1178–1189
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six-month randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft
### glutathione-oral-2015-rbc At six months, high-dose erythrocyte GSH increased within the reported 30–35% range versus baseline. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The measured compartment increased in the longer trial. organism: Human tissue_or_cell_type: 54 nonsmoking adults; immune subset experimental_model: Six-month randomized double-blind placebo-controlled trial limitations: Pool increases reported relative to baseline; NK comparison was versus placebo. Biomarkers do not prove fewer illnesses or longer life. exposure: 250 or 1000 mg/day oral GSH; one-month washout evidence_span: {"source_cache": "artifacts/glutathione-research/24791752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388", "start_char": 0, "end_char": 1596, "text_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388"} [glutathione-p24791752] Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. (2015). https://pubmed.ncbi.nlm.nih.gov/24791752/ DOI: 10.1007/s00394-014-0706-z
Complete structured claim and evidence
The yeast GCL structures identified an ATP-independent magnesium coordination site associated with the enzyme’s Mg dependence.
Mg2+ → Saccharomyces cerevisiae glutamate-cysteine ligase Gsh1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/19726687.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fd125689fc03eaf0ec433fd6b967eecc6c52c234e99e3717f10218c2c4b97625", "start_char": 0, "end_char": 1461, "text_sha256": "fd125689fc03eaf0ec433fd6b967eecc6c52c234e99e3717f10218c2c4b97625"}
experimental_model
X-ray structures and human homology model
exposure
Glutamate/MgCl2 with or without ADP
limitations
Direct metal-site observation is yeast; the human model is an inference, not a human deficiency experiment.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Saccharomyces cerevisiae enzyme; separate human model
plain_language
Magnesium has a role beyond merely being present in the assay buffer.
primary_references
[glutathione-p19726687] Mechanistic details of glutathione biosynthesis revealed by crystal structures of Saccharomyces cerevisiae glutamate cysteine ligase. (2009). https://pubmed.ncbi.nlm.nih.gov/19726687/ DOI: 10.1074/jbc.m109.025114
tissue_or_cell_type
Purified Gsh1
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 346–357
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray structures and human homology model · source_derived_draft · unverified_draft
### glutathione-gcl-magnesium The yeast GCL structures identified an ATP-independent magnesium coordination site associated with the enzyme’s Mg dependence. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium has a role beyond merely being present in the assay buffer. organism: Saccharomyces cerevisiae enzyme; separate human model tissue_or_cell_type: Purified Gsh1 experimental_model: X-ray structures and human homology model limitations: Direct metal-site observation is yeast; the human model is an inference, not a human deficiency experiment. exposure: Glutamate/MgCl2 with or without ADP evidence_span: {"source_cache": "artifacts/glutathione-research/19726687.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fd125689fc03eaf0ec433fd6b967eecc6c52c234e99e3717f10218c2c4b97625", "start_char": 0, "end_char": 1461, "text_sha256": "fd125689fc03eaf0ec433fd6b967eecc6c52c234e99e3717f10218c2c4b97625"} [glutathione-p19726687] Mechanistic details of glutathione biosynthesis revealed by crystal structures of Saccharomyces cerevisiae glutamate cysteine ligase. (2009). https://pubmed.ncbi.nlm.nih.gov/19726687/ DOI: 10.1074/jbc.m109.025114
Complete structured claim and evidence
GSH occupied the glutamate and presumed cysteine sites and disrupted ATP-site Mg coordination in the inhibited yeast structure.
GSH → Saccharomyces cerevisiae glutamate-cysteine ligase Gsh1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/20220146.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c456343cb9386a797d12af2169106d7f3b8033a5fa3882034609d3bbc26ae478", "start_char": 0, "end_char": 1382, "text_sha256": "c456343cb9386a797d12af2169106d7f3b8033a5fa3882034609d3bbc26ae478"}
experimental_model
Inhibited-enzyme crystallography
exposure
GSH and BSO-bound structures
limitations
Binding geometry is species-specific; BSO is an experimental inhibitor, not dietary depletion.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Saccharomyces cerevisiae
plain_language
The product can feed back on its own synthesis.
primary_references
[glutathione-p20220146] Structural basis for feedback and pharmacological inhibition of Saccharomyces cerevisiae glutamate cysteine ligase. (2010). https://pubmed.ncbi.nlm.nih.gov/20220146/ DOI: 10.1074/jbc.m110.104802
tissue_or_cell_type
Purified Gsh1
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 359–370
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Inhibited-enzyme crystallography · source_derived_draft · unverified_draft
### glutathione-gcl-feedback-site GSH occupied the glutamate and presumed cysteine sites and disrupted ATP-site Mg coordination in the inhibited yeast structure. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The product can feed back on its own synthesis. organism: Saccharomyces cerevisiae tissue_or_cell_type: Purified Gsh1 experimental_model: Inhibited-enzyme crystallography limitations: Binding geometry is species-specific; BSO is an experimental inhibitor, not dietary depletion. exposure: GSH and BSO-bound structures evidence_span: {"source_cache": "artifacts/glutathione-research/20220146.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c456343cb9386a797d12af2169106d7f3b8033a5fa3882034609d3bbc26ae478", "start_char": 0, "end_char": 1382, "text_sha256": "c456343cb9386a797d12af2169106d7f3b8033a5fa3882034609d3bbc26ae478"} [glutathione-p20220146] Structural basis for feedback and pharmacological inhibition of Saccharomyces cerevisiae glutamate cysteine ligase. (2010). https://pubmed.ncbi.nlm.nih.gov/20220146/ DOI: 10.1074/jbc.m110.104802
Complete structured claim and evidence
The bound BSO inhibitory species was phosphorylated on its sulfoximine nitrogen.
L-Buthionine-S-sulfoximine / BSO → Saccharomyces cerevisiae glutamate-cysteine ligase Gsh1 source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/glutathione-research/20220146.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c456343cb9386a797d12af2169106d7f3b8033a5fa3882034609d3bbc26ae478", "start_char": 0, "end_char": 1382, "text_sha256": "c456343cb9386a797d12af2169106d7f3b8033a5fa3882034609d3bbc26ae478"}
experimental_model
Inhibited-enzyme crystallography
exposure
GSH and BSO-bound structures
limitations
Binding geometry is species-specific; BSO is an experimental inhibitor, not dietary depletion.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Saccharomyces cerevisiae
plain_language
The inhibitor is chemically activated at the enzyme.
primary_references
[glutathione-p20220146] Structural basis for feedback and pharmacological inhibition of Saccharomyces cerevisiae glutamate cysteine ligase. (2010). https://pubmed.ncbi.nlm.nih.gov/20220146/ DOI: 10.1074/jbc.m110.104802
tissue_or_cell_type
Purified Gsh1
trigger_kind
machinery_impairment Imported condition classification; unverified.
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 372–383
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Inhibited-enzyme crystallography · source_derived_draft · unverified_draft
### glutathione-bso-gcl The bound BSO inhibitory species was phosphorylated on its sulfoximine nitrogen. Condition category: machinery_impairment nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The inhibitor is chemically activated at the enzyme. organism: Saccharomyces cerevisiae tissue_or_cell_type: Purified Gsh1 experimental_model: Inhibited-enzyme crystallography limitations: Binding geometry is species-specific; BSO is an experimental inhibitor, not dietary depletion. exposure: GSH and BSO-bound structures evidence_span: {"source_cache": "artifacts/glutathione-research/20220146.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c456343cb9386a797d12af2169106d7f3b8033a5fa3882034609d3bbc26ae478", "start_char": 0, "end_char": 1382, "text_sha256": "c456343cb9386a797d12af2169106d7f3b8033a5fa3882034609d3bbc26ae478"} [glutathione-p20220146] Structural basis for feedback and pharmacological inhibition of Saccharomyces cerevisiae glutamate cysteine ligase. (2010). https://pubmed.ncbi.nlm.nih.gov/20220146/ DOI: 10.1074/jbc.m110.104802
Complete structured claim and evidence
All four mutant GCLC transfectants had lower GSH than wild type in Gclc-null mouse fibroblasts; Pro414Leu was most impaired.
Human GCLC Arg127Cys, Pro158Leu, His370Leu and Pro414Leu variants → Cellular reduced-glutathione pool source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/glutathione-research/21657237.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0ef7f04eacc64f48cee159ed630014f38163f2b848bf36b99c4d371786f55d7", "start_char": 0, "end_char": 1854, "text_sha256": "d0ef7f04eacc64f48cee159ed630014f38163f2b848bf36b99c4d371786f55d7"}
experimental_model
Human variants in recombinant assays, mouse fibroblasts and yeast complementation
exposure
Four clinical GCLC variants with or without GCLM
limitations
Expression-system rescue does not establish a clinical therapy; Pro158Leu retains near-wild-type isolated kinetics.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human GCLC/GCLM; mouse and yeast hosts
plain_language
Supply can fail because the synthesis machinery is defective.
primary_references
[glutathione-p21657237] Enzymatic defects underlying hereditary glutamate cysteine ligase deficiency are mitigated by association of the catalytic and regulatory subunits. (2011). https://pubmed.ncbi.nlm.nih.gov/21657237/ DOI: 10.1021/bi200708w
tissue_or_cell_type
GCL activity and cellular GSH
trigger_kind
machinery_impairment Imported condition classification; unverified.
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 385–396
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human variants in recombinant assays, mouse fibroblasts and yeast complementation · source_derived_draft · unverified_draft
### glutathione-gclc-mutant-gsh All four mutant GCLC transfectants had lower GSH than wild type in Gclc-null mouse fibroblasts; Pro414Leu was most impaired. Condition category: machinery_impairment nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Supply can fail because the synthesis machinery is defective. organism: Human GCLC/GCLM; mouse and yeast hosts tissue_or_cell_type: GCL activity and cellular GSH experimental_model: Human variants in recombinant assays, mouse fibroblasts and yeast complementation limitations: Expression-system rescue does not establish a clinical therapy; Pro158Leu retains near-wild-type isolated kinetics. exposure: Four clinical GCLC variants with or without GCLM evidence_span: {"source_cache": "artifacts/glutathione-research/21657237.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0ef7f04eacc64f48cee159ed630014f38163f2b848bf36b99c4d371786f55d7", "start_char": 0, "end_char": 1854, "text_sha256": "d0ef7f04eacc64f48cee159ed630014f38163f2b848bf36b99c4d371786f55d7"} [glutathione-p21657237] Enzymatic defects underlying hereditary glutamate cysteine ligase deficiency are mitigated by association of the catalytic and regulatory subunits. (2011). https://pubmed.ncbi.nlm.nih.gov/21657237/ DOI: 10.1021/bi200708w
Complete structured claim and evidence
Adding GCLM largely rescued impaired activity of recombinant GCLC Arg127Cys, His370Leu and Pro414Leu.
Human glutamate-cysteine ligase modifier subunit / GCLM → Human glutamate-cysteine ligase catalytic activity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/glutathione-research/21657237.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0ef7f04eacc64f48cee159ed630014f38163f2b848bf36b99c4d371786f55d7", "start_char": 0, "end_char": 1854, "text_sha256": "d0ef7f04eacc64f48cee159ed630014f38163f2b848bf36b99c4d371786f55d7"}
experimental_model
Human variants in recombinant assays, mouse fibroblasts and yeast complementation
exposure
Four clinical GCLC variants with or without GCLM
limitations
Expression-system rescue does not establish a clinical therapy; Pro158Leu retains near-wild-type isolated kinetics.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human GCLC/GCLM; mouse and yeast hosts
plain_language
The partner subunit changed how a damaged catalytic subunit performed.
primary_references
[glutathione-p21657237] Enzymatic defects underlying hereditary glutamate cysteine ligase deficiency are mitigated by association of the catalytic and regulatory subunits. (2011). https://pubmed.ncbi.nlm.nih.gov/21657237/ DOI: 10.1021/bi200708w
tissue_or_cell_type
GCL activity and cellular GSH
trigger_kind
machinery_impairment Imported condition classification; unverified.
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 398–409
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human variants in recombinant assays, mouse fibroblasts and yeast complementation · source_derived_draft · unverified_draft
### glutathione-gclm-mutant-rescue Adding GCLM largely rescued impaired activity of recombinant GCLC Arg127Cys, His370Leu and Pro414Leu. Condition category: machinery_impairment nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The partner subunit changed how a damaged catalytic subunit performed. organism: Human GCLC/GCLM; mouse and yeast hosts tissue_or_cell_type: GCL activity and cellular GSH experimental_model: Human variants in recombinant assays, mouse fibroblasts and yeast complementation limitations: Expression-system rescue does not establish a clinical therapy; Pro158Leu retains near-wild-type isolated kinetics. exposure: Four clinical GCLC variants with or without GCLM evidence_span: {"source_cache": "artifacts/glutathione-research/21657237.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0ef7f04eacc64f48cee159ed630014f38163f2b848bf36b99c4d371786f55d7", "start_char": 0, "end_char": 1854, "text_sha256": "d0ef7f04eacc64f48cee159ed630014f38163f2b848bf36b99c4d371786f55d7"} [glutathione-p21657237] Enzymatic defects underlying hereditary glutamate cysteine ligase deficiency are mitigated by association of the catalytic and regulatory subunits. (2011). https://pubmed.ncbi.nlm.nih.gov/21657237/ DOI: 10.1021/bi200708w
Complete structured claim and evidence
Six tested GSS variants reduced Vmax to 2–27% of wild-type activity.
Human GSS L188P, D219A, D219G, Y270C, Y270H and R283C variants → Human glutathione synthetase catalytic activity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/glutathione-research/15056072.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eba1361a80a1f5021b9ca1c841eb5a6f8cc0e79302f68d30a09273debe3f6ee1", "start_char": 0, "end_char": 1151, "text_sha256": "eba1361a80a1f5021b9ca1c841eb5a6f8cc0e79302f68d30a09273debe3f6ee1"}
experimental_model
Recombinant patient-associated variant kinetics
exposure
Seven missense variants versus wild type
limitations
Variants differ; P314L was kinetically neutral in this assay. Clinical severity cannot be read directly from Vmax.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human GSS expressed in E. coli
plain_language
The last assembly step can be the bottleneck.
primary_references
[glutathione-p15056072] Human hereditary glutathione synthetase deficiency: kinetic properties of mutant enzymes. (2004). https://pubmed.ncbi.nlm.nih.gov/15056072/ DOI: 10.1042/bj20040114
tissue_or_cell_type
Purified enzymes
trigger_kind
machinery_impairment Imported condition classification; unverified.
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 411–422
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant patient-associated variant kinetics · source_derived_draft · unverified_draft
### glutathione-gss-variants Six tested GSS variants reduced Vmax to 2–27% of wild-type activity. Condition category: machinery_impairment nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The last assembly step can be the bottleneck. organism: Human GSS expressed in E. coli tissue_or_cell_type: Purified enzymes experimental_model: Recombinant patient-associated variant kinetics limitations: Variants differ; P314L was kinetically neutral in this assay. Clinical severity cannot be read directly from Vmax. exposure: Seven missense variants versus wild type evidence_span: {"source_cache": "artifacts/glutathione-research/15056072.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eba1361a80a1f5021b9ca1c841eb5a6f8cc0e79302f68d30a09273debe3f6ee1", "start_char": 0, "end_char": 1151, "text_sha256": "eba1361a80a1f5021b9ca1c841eb5a6f8cc0e79302f68d30a09273debe3f6ee1"} [glutathione-p15056072] Human hereditary glutathione synthetase deficiency: kinetic properties of mutant enzymes. (2004). https://pubmed.ncbi.nlm.nih.gov/15056072/ DOI: 10.1042/bj20040114
Complete structured claim and evidence
GSS P314L had no major effect on the tested kinetic parameters and was classified as neutral by the investigators.
Human GSS Pro314Leu variant → Human glutathione synthetase catalytic activity source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/15056072.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eba1361a80a1f5021b9ca1c841eb5a6f8cc0e79302f68d30a09273debe3f6ee1", "start_char": 0, "end_char": 1151, "text_sha256": "eba1361a80a1f5021b9ca1c841eb5a6f8cc0e79302f68d30a09273debe3f6ee1"}
experimental_model
Recombinant patient-associated variant kinetics
exposure
Seven missense variants versus wild type
limitations
Variants differ; P314L was kinetically neutral in this assay. Clinical severity cannot be read directly from Vmax.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human GSS expressed in E. coli
plain_language
A sequence difference did not automatically mean enzyme failure.
primary_references
[glutathione-p15056072] Human hereditary glutathione synthetase deficiency: kinetic properties of mutant enzymes. (2004). https://pubmed.ncbi.nlm.nih.gov/15056072/ DOI: 10.1042/bj20040114
tissue_or_cell_type
Purified enzymes
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 424–435
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant patient-associated variant kinetics · source_derived_draft · unverified_draft
### glutathione-gss-p314l-null GSS P314L had no major effect on the tested kinetic parameters and was classified as neutral by the investigators. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: A sequence difference did not automatically mean enzyme failure. organism: Human GSS expressed in E. coli tissue_or_cell_type: Purified enzymes experimental_model: Recombinant patient-associated variant kinetics limitations: Variants differ; P314L was kinetically neutral in this assay. Clinical severity cannot be read directly from Vmax. exposure: Seven missense variants versus wild type evidence_span: {"source_cache": "artifacts/glutathione-research/15056072.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eba1361a80a1f5021b9ca1c841eb5a6f8cc0e79302f68d30a09273debe3f6ee1", "start_char": 0, "end_char": 1151, "text_sha256": "eba1361a80a1f5021b9ca1c841eb5a6f8cc0e79302f68d30a09273debe3f6ee1"} [glutathione-p15056072] Human hereditary glutathione synthetase deficiency: kinetic properties of mutant enzymes. (2004). https://pubmed.ncbi.nlm.nih.gov/15056072/ DOI: 10.1042/bj20040114
Complete structured claim and evidence
The lesion localized to GSS; findings supported excess gamma-glutamylcysteine-derived 5-oxoproline production beyond disposal capacity.
GSS-deficient tissues from the two sisters studied in 1974 → 5-Oxoproline overproduction and urinary excretion in inherited GSS deficiency source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/glutathione-research/4152248.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "67120c198b8519f539205ac8148f02ffaf3ae37dc26810a7181cb18887db51d5", "start_char": 0, "end_char": 750, "text_sha256": "67120c198b8519f539205ac8148f02ffaf3ae37dc26810a7181cb18887db51d5"}
experimental_model
Enzyme studies in two affected sisters
exposure
Inherited 5-oxoprolinuria
limitations
Small historical disease study; overproduction mechanism is the authors’ interpretation, not a universal cause of acidosis.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
A blocked assembly pathway can also accumulate a side product.
primary_references
[glutathione-p4152248] Glutathione synthetase deficiency, an inborn error of metabolism involving the gamma-glutamyl cycle in patients with 5-oxoprolinuria (pyroglutamic aciduria). (1974). https://pubmed.ncbi.nlm.nih.gov/4152248/ DOI: 10.1073/pnas.71.6.2505
tissue_or_cell_type
Placenta, fibroblasts and erythrocytes
trigger_kind
machinery_impairment Imported condition classification; unverified.
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 437–448
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Enzyme studies in two affected sisters · source_derived_draft · unverified_draft
### glutathione-gss-pyroglutamate The lesion localized to GSS; findings supported excess gamma-glutamylcysteine-derived 5-oxoproline production beyond disposal capacity. Condition category: machinery_impairment nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: A blocked assembly pathway can also accumulate a side product. organism: Human tissue_or_cell_type: Placenta, fibroblasts and erythrocytes experimental_model: Enzyme studies in two affected sisters limitations: Small historical disease study; overproduction mechanism is the authors’ interpretation, not a universal cause of acidosis. exposure: Inherited 5-oxoprolinuria evidence_span: {"source_cache": "artifacts/glutathione-research/4152248.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "67120c198b8519f539205ac8148f02ffaf3ae37dc26810a7181cb18887db51d5", "start_char": 0, "end_char": 750, "text_sha256": "67120c198b8519f539205ac8148f02ffaf3ae37dc26810a7181cb18887db51d5"} [glutathione-p4152248] Glutathione synthetase deficiency, an inborn error of metabolism involving the gamma-glutamyl cycle in patients with 5-oxoprolinuria (pyroglutamic aciduria). (1974). https://pubmed.ncbi.nlm.nih.gov/4152248/ DOI: 10.1073/pnas.71.6.2505
Complete structured claim and evidence
SLC25A39 loss reduced mitochondrial GSH abundance.
SLC25A39-knockout mammalian cells → Mammalian mitochondrial reduced-glutathione pool source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/glutathione-research/34707288.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5", "start_char": 0, "end_char": 1450, "text_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5"}
experimental_model
Organelle metabolomics, genetics and targeted synthesis rescue
exposure
SLC25A39 loss, A39/A40 double loss and targeted GshF
limitations
Mitochondrial versus total-cell pools differ; engineered synthesis rescue is not oral supplementation.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Mammalian cells; separate mouse erythropoiesis experiments
plain_language
The affected compartment lost its supply.
primary_references
[glutathione-p34707288] SLC25A39 is necessary for mitochondrial glutathione import in mammalian cells. (2021). https://pubmed.ncbi.nlm.nih.gov/34707288/ DOI: 10.1038/s41586-021-04025-w
tissue_or_cell_type
Mitochondria
trigger_kind
machinery_impairment Imported condition classification; unverified.
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 463–474
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Organelle metabolomics, genetics and targeted synthesis rescue · source_derived_draft · unverified_draft
### glutathione-a39-pool SLC25A39 loss reduced mitochondrial GSH abundance. Condition category: machinery_impairment nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The affected compartment lost its supply. organism: Mammalian cells; separate mouse erythropoiesis experiments tissue_or_cell_type: Mitochondria experimental_model: Organelle metabolomics, genetics and targeted synthesis rescue limitations: Mitochondrial versus total-cell pools differ; engineered synthesis rescue is not oral supplementation. exposure: SLC25A39 loss, A39/A40 double loss and targeted GshF evidence_span: {"source_cache": "artifacts/glutathione-research/34707288.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5", "start_char": 0, "end_char": 1450, "text_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5"} [glutathione-p34707288] SLC25A39 is necessary for mitochondrial glutathione import in mammalian cells. (2021). https://pubmed.ncbi.nlm.nih.gov/34707288/ DOI: 10.1038/s41586-021-04025-w
Complete structured claim and evidence
Combined A39/A40 loss impaired activity and stability of iron-sulfur proteins.
Mammalian SLC25A39/SLC25A40 double-loss cells → Iron-sulfur protein activity and stability in A39/A40-loss cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/glutathione-research/34707288.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5", "start_char": 0, "end_char": 1450, "text_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5"}
experimental_model
Organelle metabolomics, genetics and targeted synthesis rescue
exposure
SLC25A39 loss, A39/A40 double loss and targeted GshF
limitations
Mitochondrial versus total-cell pools differ; engineered synthesis rescue is not oral supplementation.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Mammalian cells; separate mouse erythropoiesis experiments
plain_language
Glutathione availability connects to cofactor construction as well as oxidation control.
primary_references
[glutathione-p34707288] SLC25A39 is necessary for mitochondrial glutathione import in mammalian cells. (2021). https://pubmed.ncbi.nlm.nih.gov/34707288/ DOI: 10.1038/s41586-021-04025-w
tissue_or_cell_type
Mitochondria
trigger_kind
machinery_impairment Imported condition classification; unverified.
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 489–500
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Organelle metabolomics, genetics and targeted synthesis rescue · source_derived_draft · unverified_draft
### glutathione-a39-a40-fes Combined A39/A40 loss impaired activity and stability of iron-sulfur proteins. Condition category: machinery_impairment nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione availability connects to cofactor construction as well as oxidation control. organism: Mammalian cells; separate mouse erythropoiesis experiments tissue_or_cell_type: Mitochondria experimental_model: Organelle metabolomics, genetics and targeted synthesis rescue limitations: Mitochondrial versus total-cell pools differ; engineered synthesis rescue is not oral supplementation. exposure: SLC25A39 loss, A39/A40 double loss and targeted GshF evidence_span: {"source_cache": "artifacts/glutathione-research/34707288.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5", "start_char": 0, "end_char": 1450, "text_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5"} [glutathione-p34707288] SLC25A39 is necessary for mitochondrial glutathione import in mammalian cells. (2021). https://pubmed.ncbi.nlm.nih.gov/34707288/ DOI: 10.1038/s41586-021-04025-w
Complete structured claim and evidence
Targeted bacterial GshF enabled mitochondrial GSH synthesis and ameliorated proliferative defects.
Engineered mitochondrially targeted bacterial GshF in mammalian cells → Proliferation of mitochondrial-GSH-depleted mammalian cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/glutathione-research/34707288.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5", "start_char": 0, "end_char": 1450, "text_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5"}
experimental_model
Organelle metabolomics, genetics and targeted synthesis rescue
exposure
SLC25A39 loss, A39/A40 double loss and targeted GshF
limitations
Mitochondrial versus total-cell pools differ; engineered synthesis rescue is not oral supplementation.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Mammalian cells; separate mouse erythropoiesis experiments
plain_language
Producing glutathione inside mitochondria bypassed the import problem experimentally.
primary_references
[glutathione-p34707288] SLC25A39 is necessary for mitochondrial glutathione import in mammalian cells. (2021). https://pubmed.ncbi.nlm.nih.gov/34707288/ DOI: 10.1038/s41586-021-04025-w
tissue_or_cell_type
Mitochondria
trigger_kind
machinery_impairment Imported condition classification; unverified.
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 502–513
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Organelle metabolomics, genetics and targeted synthesis rescue · source_derived_draft · unverified_draft
### glutathione-mito-gshf-rescue Targeted bacterial GshF enabled mitochondrial GSH synthesis and ameliorated proliferative defects. Condition category: machinery_impairment nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Producing glutathione inside mitochondria bypassed the import problem experimentally. organism: Mammalian cells; separate mouse erythropoiesis experiments tissue_or_cell_type: Mitochondria experimental_model: Organelle metabolomics, genetics and targeted synthesis rescue limitations: Mitochondrial versus total-cell pools differ; engineered synthesis rescue is not oral supplementation. exposure: SLC25A39 loss, A39/A40 double loss and targeted GshF evidence_span: {"source_cache": "artifacts/glutathione-research/34707288.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5", "start_char": 0, "end_char": 1450, "text_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5"} [glutathione-p34707288] SLC25A39 is necessary for mitochondrial glutathione import in mammalian cells. (2021). https://pubmed.ncbi.nlm.nih.gov/34707288/ DOI: 10.1038/s41586-021-04025-w
Complete structured claim and evidence
An independent CRISPR/transport study identified SLC25A39 as critical for mitochondrial GSH import.
Human mitochondrial glutathione carrier SLC25A39 → Mammalian mitochondrial glutathione import source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/35513392.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "000d49d8bad7e173d95c214f6cb2bf2ea84b9e4af231687687d1aa703cdeaff7", "start_char": 0, "end_char": 1457, "text_sha256": "000d49d8bad7e173d95c214f6cb2bf2ea84b9e4af231687687d1aa703cdeaff7"}
experimental_model
Paired CRISPR screen and mitochondrial transport assays
exposure
2016 single/pair perturbations across four metabolic states
limitations
Genetic buffering depends on metabolic conditions; it is not evidence that iron supplementation corrects low GSH.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human experimental cells
plain_language
A second study supported the carrier assignment.
primary_references
[glutathione-p35513392] Combinatorial GxGxE CRISPR screen identifies SLC25A39 in mitochondrial glutathione transport linking iron homeostasis to OXPHOS. (2022). https://pubmed.ncbi.nlm.nih.gov/35513392/ DOI: 10.1038/s41467-022-30126-9
tissue_or_cell_type
Mitochondrial transport and respiration
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 515–526
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Paired CRISPR screen and mitochondrial transport assays · source_derived_draft · unverified_draft
### glutathione-a39-independent An independent CRISPR/transport study identified SLC25A39 as critical for mitochondrial GSH import. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second study supported the carrier assignment. organism: Human experimental cells tissue_or_cell_type: Mitochondrial transport and respiration experimental_model: Paired CRISPR screen and mitochondrial transport assays limitations: Genetic buffering depends on metabolic conditions; it is not evidence that iron supplementation corrects low GSH. exposure: 2016 single/pair perturbations across four metabolic states evidence_span: {"source_cache": "artifacts/glutathione-research/35513392.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "000d49d8bad7e173d95c214f6cb2bf2ea84b9e4af231687687d1aa703cdeaff7", "start_char": 0, "end_char": 1457, "text_sha256": "000d49d8bad7e173d95c214f6cb2bf2ea84b9e4af231687687d1aa703cdeaff7"} [glutathione-p35513392] Combinatorial GxGxE CRISPR screen identifies SLC25A39 in mitochondrial glutathione transport linking iron homeostasis to OXPHOS. (2022). https://pubmed.ncbi.nlm.nih.gov/35513392/ DOI: 10.1038/s41467-022-30126-9
Complete structured claim and evidence
A39-mediated GSH homeostasis and A37-mediated iron uptake jointly supported OXPHOS in the genetic-interaction system.
Human mitochondrial glutathione carrier SLC25A39 → Human mitoferrin-1 / SLC25A37 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/35513392.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "000d49d8bad7e173d95c214f6cb2bf2ea84b9e4af231687687d1aa703cdeaff7", "start_char": 0, "end_char": 1457, "text_sha256": "000d49d8bad7e173d95c214f6cb2bf2ea84b9e4af231687687d1aa703cdeaff7"}
experimental_model
Paired CRISPR screen and mitochondrial transport assays
exposure
2016 single/pair perturbations across four metabolic states
limitations
Genetic buffering depends on metabolic conditions; it is not evidence that iron supplementation corrects low GSH.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human experimental cells
plain_language
Iron delivery and glutathione delivery met at mitochondrial energy production.
primary_references
[glutathione-p35513392] Combinatorial GxGxE CRISPR screen identifies SLC25A39 in mitochondrial glutathione transport linking iron homeostasis to OXPHOS. (2022). https://pubmed.ncbi.nlm.nih.gov/35513392/ DOI: 10.1038/s41467-022-30126-9
tissue_or_cell_type
Mitochondrial transport and respiration
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 528–539
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Paired CRISPR screen and mitochondrial transport assays · source_derived_draft · unverified_draft
### glutathione-a39-iron-oxphos A39-mediated GSH homeostasis and A37-mediated iron uptake jointly supported OXPHOS in the genetic-interaction system. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron delivery and glutathione delivery met at mitochondrial energy production. organism: Human experimental cells tissue_or_cell_type: Mitochondrial transport and respiration experimental_model: Paired CRISPR screen and mitochondrial transport assays limitations: Genetic buffering depends on metabolic conditions; it is not evidence that iron supplementation corrects low GSH. exposure: 2016 single/pair perturbations across four metabolic states evidence_span: {"source_cache": "artifacts/glutathione-research/35513392.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "000d49d8bad7e173d95c214f6cb2bf2ea84b9e4af231687687d1aa703cdeaff7", "start_char": 0, "end_char": 1457, "text_sha256": "000d49d8bad7e173d95c214f6cb2bf2ea84b9e4af231687687d1aa703cdeaff7"} [glutathione-p35513392] Combinatorial GxGxE CRISPR screen identifies SLC25A39 in mitochondrial glutathione transport linking iron homeostasis to OXPHOS. (2022). https://pubmed.ncbi.nlm.nih.gov/35513392/ DOI: 10.1038/s41467-022-30126-9
Complete structured claim and evidence
AFG3L2 mediated SLC25A39 degradation through matrix loop 1.
Human mitochondrial m-AAA protease AFG3L2 → Human mitochondrial glutathione carrier SLC25A39 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/38157846.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8910cd64daf32714af4c954a4781163c2c5be3270e58eba14f7ff481e8a2cc71", "start_char": 0, "end_char": 1145, "text_sha256": "8910cd64daf32714af4c954a4781163c2c5be3270e58eba14f7ff481e8a2cc71"}
experimental_model
Protein-interaction proteomics, knockout and neuronal regulation
exposure
AFG3L2 deletion and iron-sulfur sensing experiments
limitations
Protein-turnover regulation; no quantitative intake requirement is inferred.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human carrier in mammalian systems
plain_language
The cell regulates carrier abundance by breaking down the protein.
primary_references
[glutathione-p38157846] Dual regulation of SLC25A39 by AFG3L2 and iron controls mitochondrial glutathione homeostasis. (2024). https://pubmed.ncbi.nlm.nih.gov/38157846/ DOI: 10.1016/j.molcel.2023.12.008
tissue_or_cell_type
Mitochondrial matrix-facing loop
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 541–552
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Protein-interaction proteomics, knockout and neuronal regulation · source_derived_draft · unverified_draft
### glutathione-afg3l2-a39 AFG3L2 mediated SLC25A39 degradation through matrix loop 1. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cell regulates carrier abundance by breaking down the protein. organism: Human carrier in mammalian systems tissue_or_cell_type: Mitochondrial matrix-facing loop experimental_model: Protein-interaction proteomics, knockout and neuronal regulation limitations: Protein-turnover regulation; no quantitative intake requirement is inferred. exposure: AFG3L2 deletion and iron-sulfur sensing experiments evidence_span: {"source_cache": "artifacts/glutathione-research/38157846.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8910cd64daf32714af4c954a4781163c2c5be3270e58eba14f7ff481e8a2cc71", "start_char": 0, "end_char": 1145, "text_sha256": "8910cd64daf32714af4c954a4781163c2c5be3270e58eba14f7ff481e8a2cc71"} [glutathione-p38157846] Dual regulation of SLC25A39 by AFG3L2 and iron controls mitochondrial glutathione homeostasis. (2024). https://pubmed.ncbi.nlm.nih.gov/38157846/ DOI: 10.1016/j.molcel.2023.12.008
Complete structured claim and evidence
Four matrix cysteines mediated iron-sulfur sensing that inhibited A39 degradation.
SLC25A39 matrix-cysteine iron-sulfur sensing → Human SLC25A39 protein degradation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/38157846.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8910cd64daf32714af4c954a4781163c2c5be3270e58eba14f7ff481e8a2cc71", "start_char": 0, "end_char": 1145, "text_sha256": "8910cd64daf32714af4c954a4781163c2c5be3270e58eba14f7ff481e8a2cc71"}
experimental_model
Protein-interaction proteomics, knockout and neuronal regulation
exposure
AFG3L2 deletion and iron-sulfur sensing experiments
limitations
Protein-turnover regulation; no quantitative intake requirement is inferred.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human carrier in mammalian systems
plain_language
A cofactor-related signal changed how long the carrier persisted.
primary_references
[glutathione-p38157846] Dual regulation of SLC25A39 by AFG3L2 and iron controls mitochondrial glutathione homeostasis. (2024). https://pubmed.ncbi.nlm.nih.gov/38157846/ DOI: 10.1016/j.molcel.2023.12.008
tissue_or_cell_type
Mitochondrial matrix-facing loop
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 554–565
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Protein-interaction proteomics, knockout and neuronal regulation · source_derived_draft · unverified_draft
### glutathione-a39-fes-stability Four matrix cysteines mediated iron-sulfur sensing that inhibited A39 degradation. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: A cofactor-related signal changed how long the carrier persisted. organism: Human carrier in mammalian systems tissue_or_cell_type: Mitochondrial matrix-facing loop experimental_model: Protein-interaction proteomics, knockout and neuronal regulation limitations: Protein-turnover regulation; no quantitative intake requirement is inferred. exposure: AFG3L2 deletion and iron-sulfur sensing experiments evidence_span: {"source_cache": "artifacts/glutathione-research/38157846.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8910cd64daf32714af4c954a4781163c2c5be3270e58eba14f7ff481e8a2cc71", "start_char": 0, "end_char": 1145, "text_sha256": "8910cd64daf32714af4c954a4781163c2c5be3270e58eba14f7ff481e8a2cc71"} [glutathione-p38157846] Dual regulation of SLC25A39 by AFG3L2 and iron controls mitochondrial glutathione homeostasis. (2024). https://pubmed.ncbi.nlm.nih.gov/38157846/ DOI: 10.1016/j.molcel.2023.12.008
Complete structured claim and evidence
ATF4-responsive promoter elements supported human CHAC1 transcription in reporter experiments.
Human activating transcription factor 4 / ATF4 → Human CHAC1 promoter activity and expression source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/25931127.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a561d11e802b38659805fe90dcab499bf0f434dbe91fa5510cf1eb4efb3460b1", "start_char": 0, "end_char": 1504, "text_sha256": "a561d11e802b38659805fe90dcab499bf0f434dbe91fa5510cf1eb4efb3460b1"}
experimental_model
Human promoter reporters, binding assays and overexpression
exposure
ER stress, ATF4 and CHAC1 expression
limitations
Cell experiments; CHAC1 induction is not a dietary GSH-deficiency diagnosis.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
A stress-response factor can turn on glutathione breakdown.
primary_references
[glutathione-p25931127] Human CHAC1 Protein Degrades Glutathione, and mRNA Induction Is Regulated by the Transcription Factors ATF4 and ATF3 and a Bipartite ATF/CRE Regulatory Element. (2015). https://pubmed.ncbi.nlm.nih.gov/25931127/ DOI: 10.1074/jbc.m114.635144
tissue_or_cell_type
HEK293 and U2OS cells
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 567–578
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human promoter reporters, binding assays and overexpression · source_derived_draft · unverified_draft
### glutathione-atf4-chac1 ATF4-responsive promoter elements supported human CHAC1 transcription in reporter experiments. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: A stress-response factor can turn on glutathione breakdown. organism: Human tissue_or_cell_type: HEK293 and U2OS cells experimental_model: Human promoter reporters, binding assays and overexpression limitations: Cell experiments; CHAC1 induction is not a dietary GSH-deficiency diagnosis. exposure: ER stress, ATF4 and CHAC1 expression evidence_span: {"source_cache": "artifacts/glutathione-research/25931127.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a561d11e802b38659805fe90dcab499bf0f434dbe91fa5510cf1eb4efb3460b1", "start_char": 0, "end_char": 1504, "text_sha256": "a561d11e802b38659805fe90dcab499bf0f434dbe91fa5510cf1eb4efb3460b1"} [glutathione-p25931127] Human CHAC1 Protein Degrades Glutathione, and mRNA Induction Is Regulated by the Transcription Factors ATF4 and ATF3 and a Bipartite ATF/CRE Regulatory Element. (2015). https://pubmed.ncbi.nlm.nih.gov/25931127/ DOI: 10.1074/jbc.m114.635144
Complete structured claim and evidence
Purified human CHAC2 degraded reduced GSH with lower catalytic efficiency than CHAC1.
Human glutathione-specific gamma-glutamylcyclotransferase CHAC2 → GSH source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/27913623.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ddf397c2cb8fd60423c89cab28a0b54d124f0e34e0564a32d6bca36841530694", "start_char": 0, "end_char": 1617, "text_sha256": "ddf397c2cb8fd60423c89cab28a0b54d124f0e34e0564a32d6bca36841530694"}
experimental_model
Purified mammalian enzymes and expression comparison
exposure
CHAC1/CHAC2 substrate and kinetics comparison
limitations
Human kinetics and yeast structure are distinct; this does not establish a universal turnover rate in vivo.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human and mouse enzymes; yeast structural homolog
plain_language
A separate enzyme supports slower glutathione turnover.
primary_references
[glutathione-p27913623] ChaC2, an Enzyme for Slow Turnover of Cytosolic Glutathione. (2017). https://pubmed.ncbi.nlm.nih.gov/27913623/ DOI: 10.1074/jbc.m116.727479
tissue_or_cell_type
Cytosolic glutathione turnover
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 593–604
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified mammalian enzymes and expression comparison · source_derived_draft · unverified_draft
### glutathione-chac2-gsh Purified human CHAC2 degraded reduced GSH with lower catalytic efficiency than CHAC1. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: A separate enzyme supports slower glutathione turnover. organism: Human and mouse enzymes; yeast structural homolog tissue_or_cell_type: Cytosolic glutathione turnover experimental_model: Purified mammalian enzymes and expression comparison limitations: Human kinetics and yeast structure are distinct; this does not establish a universal turnover rate in vivo. exposure: CHAC1/CHAC2 substrate and kinetics comparison evidence_span: {"source_cache": "artifacts/glutathione-research/27913623.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ddf397c2cb8fd60423c89cab28a0b54d124f0e34e0564a32d6bca36841530694", "start_char": 0, "end_char": 1617, "text_sha256": "ddf397c2cb8fd60423c89cab28a0b54d124f0e34e0564a32d6bca36841530694"} [glutathione-p27913623] ChaC2, an Enzyme for Slow Turnover of Cytosolic Glutathione. (2017). https://pubmed.ncbi.nlm.nih.gov/27913623/ DOI: 10.1074/jbc.m116.727479
Complete structured claim and evidence
CHAC2 showed no activity against oxidized glutathione in the substrate comparison.
Human glutathione-specific gamma-glutamylcyclotransferase CHAC2 → GSSG source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/27913623.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ddf397c2cb8fd60423c89cab28a0b54d124f0e34e0564a32d6bca36841530694", "start_char": 0, "end_char": 1617, "text_sha256": "ddf397c2cb8fd60423c89cab28a0b54d124f0e34e0564a32d6bca36841530694"}
experimental_model
Purified mammalian enzymes and expression comparison
exposure
CHAC1/CHAC2 substrate and kinetics comparison
limitations
Human kinetics and yeast structure are distinct; this does not establish a universal turnover rate in vivo.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human and mouse enzymes; yeast structural homolog
plain_language
Reduced and oxidized glutathione were not interchangeable substrates.
primary_references
[glutathione-p27913623] ChaC2, an Enzyme for Slow Turnover of Cytosolic Glutathione. (2017). https://pubmed.ncbi.nlm.nih.gov/27913623/ DOI: 10.1074/jbc.m116.727479
tissue_or_cell_type
Cytosolic glutathione turnover
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 606–617
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified mammalian enzymes and expression comparison · source_derived_draft · unverified_draft
### glutathione-chac2-gssg-null CHAC2 showed no activity against oxidized glutathione in the substrate comparison. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reduced and oxidized glutathione were not interchangeable substrates. organism: Human and mouse enzymes; yeast structural homolog tissue_or_cell_type: Cytosolic glutathione turnover experimental_model: Purified mammalian enzymes and expression comparison limitations: Human kinetics and yeast structure are distinct; this does not establish a universal turnover rate in vivo. exposure: CHAC1/CHAC2 substrate and kinetics comparison evidence_span: {"source_cache": "artifacts/glutathione-research/27913623.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ddf397c2cb8fd60423c89cab28a0b54d124f0e34e0564a32d6bca36841530694", "start_char": 0, "end_char": 1617, "text_sha256": "ddf397c2cb8fd60423c89cab28a0b54d124f0e34e0564a32d6bca36841530694"} [glutathione-p27913623] ChaC2, an Enzyme for Slow Turnover of Cytosolic Glutathione. (2017). https://pubmed.ncbi.nlm.nih.gov/27913623/ DOI: 10.1074/jbc.m116.727479
Complete structured claim and evidence
CHAC1 likewise lacked activity against GSSG in this comparison.
Human glutathione-specific gamma-glutamylcyclotransferase CHAC1 → GSSG source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/27913623.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ddf397c2cb8fd60423c89cab28a0b54d124f0e34e0564a32d6bca36841530694", "start_char": 0, "end_char": 1617, "text_sha256": "ddf397c2cb8fd60423c89cab28a0b54d124f0e34e0564a32d6bca36841530694"}
experimental_model
Purified mammalian enzymes and expression comparison
exposure
CHAC1/CHAC2 substrate and kinetics comparison
limitations
Human kinetics and yeast structure are distinct; this does not establish a universal turnover rate in vivo.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human and mouse enzymes; yeast structural homolog
plain_language
Substrate identity matters even within one degradation family.
primary_references
[glutathione-p27913623] ChaC2, an Enzyme for Slow Turnover of Cytosolic Glutathione. (2017). https://pubmed.ncbi.nlm.nih.gov/27913623/ DOI: 10.1074/jbc.m116.727479
tissue_or_cell_type
Cytosolic glutathione turnover
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 619–630
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified mammalian enzymes and expression comparison · source_derived_draft · unverified_draft
### glutathione-chac1-gssg-null CHAC1 likewise lacked activity against GSSG in this comparison. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Substrate identity matters even within one degradation family. organism: Human and mouse enzymes; yeast structural homolog tissue_or_cell_type: Cytosolic glutathione turnover experimental_model: Purified mammalian enzymes and expression comparison limitations: Human kinetics and yeast structure are distinct; this does not establish a universal turnover rate in vivo. exposure: CHAC1/CHAC2 substrate and kinetics comparison evidence_span: {"source_cache": "artifacts/glutathione-research/27913623.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "ddf397c2cb8fd60423c89cab28a0b54d124f0e34e0564a32d6bca36841530694", "start_char": 0, "end_char": 1617, "text_sha256": "ddf397c2cb8fd60423c89cab28a0b54d124f0e34e0564a32d6bca36841530694"} [glutathione-p27913623] ChaC2, an Enzyme for Slow Turnover of Cytosolic Glutathione. (2017). https://pubmed.ncbi.nlm.nih.gov/27913623/ DOI: 10.1074/jbc.m116.727479
Complete structured claim and evidence
Human-GGT-expressing fibroblasts used extracellular GSH as a cysteine source in cysteine-free medium.
Human gamma-glutamyltransferase 1 / GGT1 → extracellular cysteine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/8099811.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "53a6b1a1855863d8fe1d0be289055e7cd6ca39b33e936e82dfed2d7d084c9d5b", "start_char": 0, "end_char": 984, "text_sha256": "53a6b1a1855863d8fe1d0be289055e7cd6ca39b33e936e82dfed2d7d084c9d5b"}
experimental_model
Human GGT transfection in mouse fibroblasts
exposure
Cysteine-free medium supplemented with extracellular GSH
limitations
Precursor salvage after extracellular cleavage; not proof of intact oral GSH entry into every tissue.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human GGT; NIH/3T3 host
plain_language
Breaking down glutathione outside a cell can supply building blocks inside.
primary_references
[glutathione-p8099811] Extracellular glutathione is a source of cysteine for cells that express gamma-glutamyl transpeptidase. (1993). https://pubmed.ncbi.nlm.nih.gov/8099811/ DOI: 10.1021/bi00075a026
tissue_or_cell_type
Cell surface and intracellular pools
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 632–643
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human GGT transfection in mouse fibroblasts · source_derived_draft · unverified_draft
### glutathione-ggt-cysteine Human-GGT-expressing fibroblasts used extracellular GSH as a cysteine source in cysteine-free medium. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Breaking down glutathione outside a cell can supply building blocks inside. organism: Human GGT; NIH/3T3 host tissue_or_cell_type: Cell surface and intracellular pools experimental_model: Human GGT transfection in mouse fibroblasts limitations: Precursor salvage after extracellular cleavage; not proof of intact oral GSH entry into every tissue. exposure: Cysteine-free medium supplemented with extracellular GSH evidence_span: {"source_cache": "artifacts/glutathione-research/8099811.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "53a6b1a1855863d8fe1d0be289055e7cd6ca39b33e936e82dfed2d7d084c9d5b", "start_char": 0, "end_char": 984, "text_sha256": "53a6b1a1855863d8fe1d0be289055e7cd6ca39b33e936e82dfed2d7d084c9d5b"} [glutathione-p8099811] Extracellular glutathione is a source of cysteine for cells that express gamma-glutamyl transpeptidase. (1993). https://pubmed.ncbi.nlm.nih.gov/8099811/ DOI: 10.1021/bi00075a026
Complete structured claim and evidence
GGT-positive cells replenished intracellular GSH from extracellular GSH under cysteine deprivation; GGT-negative cells did not.
Human gamma-glutamyltransferase 1 / GGT1 → Intracellular GSH replenishment in human-GGT-expressing NIH/3T3 cells source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/8099811.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "53a6b1a1855863d8fe1d0be289055e7cd6ca39b33e936e82dfed2d7d084c9d5b", "start_char": 0, "end_char": 984, "text_sha256": "53a6b1a1855863d8fe1d0be289055e7cd6ca39b33e936e82dfed2d7d084c9d5b"}
experimental_model
Human GGT transfection in mouse fibroblasts
exposure
Cysteine-free medium supplemented with extracellular GSH
limitations
Precursor salvage after extracellular cleavage; not proof of intact oral GSH entry into every tissue.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human GGT; NIH/3T3 host
plain_language
Extracellular breakdown can support intracellular rebuilding.
primary_references
[glutathione-p8099811] Extracellular glutathione is a source of cysteine for cells that express gamma-glutamyl transpeptidase. (1993). https://pubmed.ncbi.nlm.nih.gov/8099811/ DOI: 10.1021/bi00075a026
tissue_or_cell_type
Cell surface and intracellular pools
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 645–656
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human GGT transfection in mouse fibroblasts · source_derived_draft · unverified_draft
### glutathione-ggt-replenishment GGT-positive cells replenished intracellular GSH from extracellular GSH under cysteine deprivation; GGT-negative cells did not. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Extracellular breakdown can support intracellular rebuilding. organism: Human GGT; NIH/3T3 host tissue_or_cell_type: Cell surface and intracellular pools experimental_model: Human GGT transfection in mouse fibroblasts limitations: Precursor salvage after extracellular cleavage; not proof of intact oral GSH entry into every tissue. exposure: Cysteine-free medium supplemented with extracellular GSH evidence_span: {"source_cache": "artifacts/glutathione-research/8099811.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "53a6b1a1855863d8fe1d0be289055e7cd6ca39b33e936e82dfed2d7d084c9d5b", "start_char": 0, "end_char": 984, "text_sha256": "53a6b1a1855863d8fe1d0be289055e7cd6ca39b33e936e82dfed2d7d084c9d5b"} [glutathione-p8099811] Extracellular glutathione is a source of cysteine for cells that express gamma-glutamyl transpeptidase. (1993). https://pubmed.ncbi.nlm.nih.gov/8099811/ DOI: 10.1021/bi00075a026
Complete structured claim and evidence
Plasma cyst(e)ine in Ggt1-null mice was about 20% of wild type.
Ggt1-null mice in the 1996 study → Plasma cyst(e)ine in Ggt1-null mice source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/glutathione-research/8755578.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "94d2520bc0124611c649d943ab9acd9cdf73cd3cb99d66640338a57bda6f6dfb", "start_char": 0, "end_char": 1159, "text_sha256": "94d2520bc0124611c649d943ab9acd9cdf73cd3cb99d66640338a57bda6f6dfb"}
experimental_model
Targeted GGT gene disruption and NAC rescue
exposure
Ggt1-null versus wild type; oral NAC
limitations
Severe genetic salvage defect; high extracellular GSH did not mean adequate tissue stores.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Mouse
plain_language
A blocked salvage pathway reduced precursor availability.
primary_references
[glutathione-p8755578] Growth retardation and cysteine deficiency in gamma-glutamyl transpeptidase-deficient mice. (1996). https://pubmed.ncbi.nlm.nih.gov/8755578/ DOI: 10.1073/pnas.93.15.7923
tissue_or_cell_type
Plasma, urine, eye, liver and pancreas
trigger_kind
machinery_impairment Imported condition classification; unverified.
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 658–669
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Targeted GGT gene disruption and NAC rescue · source_derived_draft · unverified_draft
### glutathione-ggt-cysteine-low Plasma cyst(e)ine in Ggt1-null mice was about 20% of wild type. Condition category: machinery_impairment nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: A blocked salvage pathway reduced precursor availability. organism: Mouse tissue_or_cell_type: Plasma, urine, eye, liver and pancreas experimental_model: Targeted GGT gene disruption and NAC rescue limitations: Severe genetic salvage defect; high extracellular GSH did not mean adequate tissue stores. exposure: Ggt1-null versus wild type; oral NAC evidence_span: {"source_cache": "artifacts/glutathione-research/8755578.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "94d2520bc0124611c649d943ab9acd9cdf73cd3cb99d66640338a57bda6f6dfb", "start_char": 0, "end_char": 1159, "text_sha256": "94d2520bc0124611c649d943ab9acd9cdf73cd3cb99d66640338a57bda6f6dfb"} [glutathione-p8755578] Growth retardation and cysteine deficiency in gamma-glutamyl transpeptidase-deficient mice. (1996). https://pubmed.ncbi.nlm.nih.gov/8755578/ DOI: 10.1073/pnas.93.15.7923
Complete structured claim and evidence
Plasma GSH was about sixfold higher in Ggt1-null mice.
Ggt1-null mice in the 1996 study → Plasma glutathione in Ggt1-null mice source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/glutathione-research/8755578.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "94d2520bc0124611c649d943ab9acd9cdf73cd3cb99d66640338a57bda6f6dfb", "start_char": 0, "end_char": 1159, "text_sha256": "94d2520bc0124611c649d943ab9acd9cdf73cd3cb99d66640338a57bda6f6dfb"}
experimental_model
Targeted GGT gene disruption and NAC rescue
exposure
Ggt1-null versus wild type; oral NAC
limitations
Severe genetic salvage defect; high extracellular GSH did not mean adequate tissue stores.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Mouse
plain_language
High plasma glutathione did not rule out a metabolic defect.
primary_references
[glutathione-p8755578] Growth retardation and cysteine deficiency in gamma-glutamyl transpeptidase-deficient mice. (1996). https://pubmed.ncbi.nlm.nih.gov/8755578/ DOI: 10.1073/pnas.93.15.7923
tissue_or_cell_type
Plasma, urine, eye, liver and pancreas
trigger_kind
machinery_impairment Imported condition classification; unverified.
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 671–682
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Targeted GGT gene disruption and NAC rescue · source_derived_draft · unverified_draft
### glutathione-ggt-plasma-high Plasma GSH was about sixfold higher in Ggt1-null mice. Condition category: machinery_impairment nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: High plasma glutathione did not rule out a metabolic defect. organism: Mouse tissue_or_cell_type: Plasma, urine, eye, liver and pancreas experimental_model: Targeted GGT gene disruption and NAC rescue limitations: Severe genetic salvage defect; high extracellular GSH did not mean adequate tissue stores. exposure: Ggt1-null versus wild type; oral NAC evidence_span: {"source_cache": "artifacts/glutathione-research/8755578.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "94d2520bc0124611c649d943ab9acd9cdf73cd3cb99d66640338a57bda6f6dfb", "start_char": 0, "end_char": 1159, "text_sha256": "94d2520bc0124611c649d943ab9acd9cdf73cd3cb99d66640338a57bda6f6dfb"} [glutathione-p8755578] Growth retardation and cysteine deficiency in gamma-glutamyl transpeptidase-deficient mice. (1996). https://pubmed.ncbi.nlm.nih.gov/8755578/ DOI: 10.1073/pnas.93.15.7923
Complete structured claim and evidence
Urinary GSH was about 2500-fold higher in Ggt1-null mice.
Ggt1-null mice in the 1996 study → Urinary glutathione excretion in Ggt1-null mice source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/glutathione-research/8755578.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "94d2520bc0124611c649d943ab9acd9cdf73cd3cb99d66640338a57bda6f6dfb", "start_char": 0, "end_char": 1159, "text_sha256": "94d2520bc0124611c649d943ab9acd9cdf73cd3cb99d66640338a57bda6f6dfb"}
experimental_model
Targeted GGT gene disruption and NAC rescue
exposure
Ggt1-null versus wild type; oral NAC
limitations
Severe genetic salvage defect; high extracellular GSH did not mean adequate tissue stores.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Mouse
plain_language
Glutathione was lost rather than effectively salvaged.
primary_references
[glutathione-p8755578] Growth retardation and cysteine deficiency in gamma-glutamyl transpeptidase-deficient mice. (1996). https://pubmed.ncbi.nlm.nih.gov/8755578/ DOI: 10.1073/pnas.93.15.7923
tissue_or_cell_type
Plasma, urine, eye, liver and pancreas
trigger_kind
machinery_impairment Imported condition classification; unverified.
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 684–695
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Targeted GGT gene disruption and NAC rescue · source_derived_draft · unverified_draft
### glutathione-ggt-urine-high Urinary GSH was about 2500-fold higher in Ggt1-null mice. Condition category: machinery_impairment nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione was lost rather than effectively salvaged. organism: Mouse tissue_or_cell_type: Plasma, urine, eye, liver and pancreas experimental_model: Targeted GGT gene disruption and NAC rescue limitations: Severe genetic salvage defect; high extracellular GSH did not mean adequate tissue stores. exposure: Ggt1-null versus wild type; oral NAC evidence_span: {"source_cache": "artifacts/glutathione-research/8755578.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "94d2520bc0124611c649d943ab9acd9cdf73cd3cb99d66640338a57bda6f6dfb", "start_char": 0, "end_char": 1159, "text_sha256": "94d2520bc0124611c649d943ab9acd9cdf73cd3cb99d66640338a57bda6f6dfb"} [glutathione-p8755578] Growth retardation and cysteine deficiency in gamma-glutamyl transpeptidase-deficient mice. (1996). https://pubmed.ncbi.nlm.nih.gov/8755578/ DOI: 10.1073/pnas.93.15.7923
Complete structured claim and evidence
Oral NAC restored normal growth rates in the Ggt1-null mice.
N-Acetyl-L-cysteine → Growth rate of Ggt1-null mice source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/glutathione-research/8755578.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "94d2520bc0124611c649d943ab9acd9cdf73cd3cb99d66640338a57bda6f6dfb", "start_char": 0, "end_char": 1159, "text_sha256": "94d2520bc0124611c649d943ab9acd9cdf73cd3cb99d66640338a57bda6f6dfb"}
experimental_model
Targeted GGT gene disruption and NAC rescue
exposure
Ggt1-null versus wild type; oral NAC
limitations
Severe genetic salvage defect; high extracellular GSH did not mean adequate tissue stores.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Mouse
plain_language
Providing an alternative cysteine source bypassed part of the salvage problem.
primary_references
[glutathione-p8755578] Growth retardation and cysteine deficiency in gamma-glutamyl transpeptidase-deficient mice. (1996). https://pubmed.ncbi.nlm.nih.gov/8755578/ DOI: 10.1073/pnas.93.15.7923
tissue_or_cell_type
Plasma, urine, eye, liver and pancreas
trigger_kind
machinery_impairment Imported condition classification; unverified.
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 710–721
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Targeted GGT gene disruption and NAC rescue · source_derived_draft · unverified_draft
### glutathione-ggt-nac-rescue Oral NAC restored normal growth rates in the Ggt1-null mice. Condition category: machinery_impairment nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Providing an alternative cysteine source bypassed part of the salvage problem. organism: Mouse tissue_or_cell_type: Plasma, urine, eye, liver and pancreas experimental_model: Targeted GGT gene disruption and NAC rescue limitations: Severe genetic salvage defect; high extracellular GSH did not mean adequate tissue stores. exposure: Ggt1-null versus wild type; oral NAC evidence_span: {"source_cache": "artifacts/glutathione-research/8755578.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "94d2520bc0124611c649d943ab9acd9cdf73cd3cb99d66640338a57bda6f6dfb", "start_char": 0, "end_char": 1159, "text_sha256": "94d2520bc0124611c649d943ab9acd9cdf73cd3cb99d66640338a57bda6f6dfb"} [glutathione-p8755578] Growth retardation and cysteine deficiency in gamma-glutamyl transpeptidase-deficient mice. (1996). https://pubmed.ncbi.nlm.nih.gov/8755578/ DOI: 10.1073/pnas.93.15.7923
Complete structured claim and evidence
MRP1 mediated ATP-dependent GSSG transport; the HeLa-vesicle Km was 93 ± 26 micromolar.
Human multidrug resistance-associated protein 1 / ABCC1 / MRP1 → ATP-dependent MRP1 glutathione-disulfide transport source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/8670053.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9178e466ea8bd18f0957cc65594934ec1681ad7483e6ac64d79c4b8d8ca2afc3", "start_char": 0, "end_char": 1433, "text_sha256": "9178e466ea8bd18f0957cc65594934ec1681ad7483e6ac64d79c4b8d8ca2afc3"}
experimental_model
Membrane-vesicle transport assays
exposure
ATP-dependent GSSG uptake into vesicles
limitations
Vesicle uptake reflects cellular export; the GSH null result applies specifically to the tested 100 micromolar condition.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human HL60 and HeLa systems
plain_language
Oxidized glutathione can be exported instead of recycled locally.
primary_references
[glutathione-p8670053] ATP-dependent glutathione disulphide transport mediated by the MRP gene-encoded conjugate export pump. (1996). https://pubmed.ncbi.nlm.nih.gov/8670053/ DOI: 10.1042/bj3140433
tissue_or_cell_type
MRP-overexpressing membranes
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 723–734
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Membrane-vesicle transport assays · source_derived_draft · unverified_draft
### glutathione-mrp-gssg MRP1 mediated ATP-dependent GSSG transport; the HeLa-vesicle Km was 93 ± 26 micromolar. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Oxidized glutathione can be exported instead of recycled locally. organism: Human HL60 and HeLa systems tissue_or_cell_type: MRP-overexpressing membranes experimental_model: Membrane-vesicle transport assays limitations: Vesicle uptake reflects cellular export; the GSH null result applies specifically to the tested 100 micromolar condition. exposure: ATP-dependent GSSG uptake into vesicles evidence_span: {"source_cache": "artifacts/glutathione-research/8670053.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "9178e466ea8bd18f0957cc65594934ec1681ad7483e6ac64d79c4b8d8ca2afc3", "start_char": 0, "end_char": 1433, "text_sha256": "9178e466ea8bd18f0957cc65594934ec1681ad7483e6ac64d79c4b8d8ca2afc3"} [glutathione-p8670053] ATP-dependent glutathione disulphide transport mediated by the MRP gene-encoded conjugate export pump. (1996). https://pubmed.ncbi.nlm.nih.gov/8670053/ DOI: 10.1042/bj3140433
Complete structured claim and evidence
Diethyl maleate induced xCT expression and increased cystine uptake in U87 cells.
SLC7A11 → cystine uptake source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/11406111.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e7118afd8c6055ed926ee24dbb7a07538f676163d605115ae0d32d49fbef7fdc", "start_char": 0, "end_char": 1364, "text_sha256": "e7118afd8c6055ed926ee24dbb7a07538f676163d605115ae0d32d49fbef7fdc"}
experimental_model
Human xCT expression and oxidative-stress response
exposure
hxCTb with 4F2hc; diethyl maleate challenge
limitations
Sodium independence belongs to this transporter; other cysteine-entry routes differ.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human transporter; Xenopus expression host
plain_language
The cells adjusted precursor uptake during the experimental challenge.
primary_references
[glutathione-p11406111] Human cystine/glutamate transporter: cDNA cloning and upregulation by oxidative stress in glioma cells. (2001). https://pubmed.ncbi.nlm.nih.gov/11406111/ DOI: 10.1016/s0005-2736(01)00338-8
tissue_or_cell_type
Oocyte membranes and human U87 glioma cells
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 749–760
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human xCT expression and oxidative-stress response · source_derived_draft · unverified_draft
### glutathione-xct-stress Diethyl maleate induced xCT expression and increased cystine uptake in U87 cells. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cells adjusted precursor uptake during the experimental challenge. organism: Human transporter; Xenopus expression host tissue_or_cell_type: Oocyte membranes and human U87 glioma cells experimental_model: Human xCT expression and oxidative-stress response limitations: Sodium independence belongs to this transporter; other cysteine-entry routes differ. exposure: hxCTb with 4F2hc; diethyl maleate challenge evidence_span: {"source_cache": "artifacts/glutathione-research/11406111.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e7118afd8c6055ed926ee24dbb7a07538f676163d605115ae0d32d49fbef7fdc", "start_char": 0, "end_char": 1364, "text_sha256": "e7118afd8c6055ed926ee24dbb7a07538f676163d605115ae0d32d49fbef7fdc"} [glutathione-p11406111] Human cystine/glutamate transporter: cDNA cloning and upregulation by oxidative stress in glioma cells. (2001). https://pubmed.ncbi.nlm.nih.gov/11406111/ DOI: 10.1016/s0005-2736(01)00338-8
Complete structured claim and evidence
Structural-site NADP+ binding ordered the G6PD C-terminal region and supported substrate binding and catalysis.
NADP+ → Human G6PD glucose-6-phosphate binding and catalysis source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/35858355.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "02c2d0e880b17ab304fab0854064813ffec5fa9e647b978a083aa88fbf8a38f0", "start_char": 0, "end_char": 1328, "text_sha256": "02c2d0e880b17ab304fab0854064813ffec5fa9e647b978a083aa88fbf8a38f0"}
experimental_model
Cryo-EM and structural comparison
exposure
Ligand-free and NADP/G6P-bound states
limitations
Structural NADP and catalytic NADP are different sites; enzyme activity is not a niacin-treatment trial.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
The same coenzyme also has a distinct structural regulatory role.
primary_references
[glutathione-p35858355] Allosteric role of a structural NADP+ molecule in glucose-6-phosphate dehydrogenase activity. (2022). https://pubmed.ncbi.nlm.nih.gov/35858355/ DOI: 10.1073/pnas.2119695119
tissue_or_cell_type
Purified wild-type G6PD and D200N
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 775–786
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM and structural comparison · source_derived_draft · unverified_draft
### glutathione-g6pd-structural-nadp Structural-site NADP+ binding ordered the G6PD C-terminal region and supported substrate binding and catalysis. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same coenzyme also has a distinct structural regulatory role. organism: Human tissue_or_cell_type: Purified wild-type G6PD and D200N experimental_model: Cryo-EM and structural comparison limitations: Structural NADP and catalytic NADP are different sites; enzyme activity is not a niacin-treatment trial. exposure: Ligand-free and NADP/G6P-bound states evidence_span: {"source_cache": "artifacts/glutathione-research/35858355.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "02c2d0e880b17ab304fab0854064813ffec5fa9e647b978a083aa88fbf8a38f0", "start_char": 0, "end_char": 1328, "text_sha256": "02c2d0e880b17ab304fab0854064813ffec5fa9e647b978a083aa88fbf8a38f0"} [glutathione-p35858355] Allosteric role of a structural NADP+ molecule in glucose-6-phosphate dehydrogenase activity. (2022). https://pubmed.ncbi.nlm.nih.gov/35858355/ DOI: 10.1073/pnas.2119695119
Complete structured claim and evidence
Apo-GLRX5 reduced glutathione mixed disulfides about 100 times more slowly than GLRX2.
Human mitochondrial glutaredoxin 5 / GLRX5 → Human glutaredoxin 2 / GLRX2 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/21029046.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bc7e33127eee3685d1f90bff5a83334d68ac0ee3f73eeb67e4a9e189c5ba20b2", "start_char": 0, "end_char": 1468, "text_sha256": "bc7e33127eee3685d1f90bff5a83334d68ac0ee3f73eeb67e4a9e189c5ba20b2"}
experimental_model
Crystallography, solution oligomers and biochemical assays
exposure
Iron-sulfur/GSH complex and disulfide assays
limitations
The structural cluster complex is not a dietary-iron requirement or proof of supplement synergy.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human GLRX5
plain_language
Related glutaredoxins are not functionally interchangeable.
primary_references
[glutathione-p21029046] The crystal structure of human GLRX5: iron-sulfur cluster co-ordination, tetrameric assembly and monomer activity. (2011). https://pubmed.ncbi.nlm.nih.gov/21029046/ DOI: 10.1042/bj20101286
tissue_or_cell_type
Purified holo and apo protein
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 801–812
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystallography, solution oligomers and biochemical assays · source_derived_draft · unverified_draft
### glutathione-glrx5-disulfide-rate Apo-GLRX5 reduced glutathione mixed disulfides about 100 times more slowly than GLRX2. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Related glutaredoxins are not functionally interchangeable. organism: Human GLRX5 tissue_or_cell_type: Purified holo and apo protein experimental_model: Crystallography, solution oligomers and biochemical assays limitations: The structural cluster complex is not a dietary-iron requirement or proof of supplement synergy. exposure: Iron-sulfur/GSH complex and disulfide assays evidence_span: {"source_cache": "artifacts/glutathione-research/21029046.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "bc7e33127eee3685d1f90bff5a83334d68ac0ee3f73eeb67e4a9e189c5ba20b2", "start_char": 0, "end_char": 1468, "text_sha256": "bc7e33127eee3685d1f90bff5a83334d68ac0ee3f73eeb67e4a9e189c5ba20b2"} [glutathione-p21029046] The crystal structure of human GLRX5: iron-sulfur cluster co-ordination, tetrameric assembly and monomer activity. (2011). https://pubmed.ncbi.nlm.nih.gov/21029046/ DOI: 10.1042/bj20101286
Complete structured claim and evidence
GLRX2 reduced glutathionylated substrates with lower rate but higher affinity than GLRX1, giving similar catalytic efficiency.
Human glutaredoxin 2 / GLRX2 → Human GLRX2-mediated protein deglutathionylation source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/14676218.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a7399b7d035bd3815c30362449b7986dea08873c824e05506d7db627a71daa84", "start_char": 0, "end_char": 1398, "text_sha256": "a7399b7d035bd3815c30362449b7986dea08873c824e05506d7db627a71daa84"}
experimental_model
Purified human glutaredoxin kinetics and mutants
exposure
GSH or NADPH/thioredoxin-reductase donor systems
limitations
Biochemical electron-donor alternatives; no claim that all cellular GLRX2 uses one route.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human GLRX1/GLRX2
plain_language
Glutathione attached to a protein can be removed enzymatically.
primary_references
[glutathione-p14676218] Human mitochondrial glutaredoxin reduces S-glutathionylated proteins with high affinity accepting electrons from either glutathione or thioredoxin reductase. (2004). https://pubmed.ncbi.nlm.nih.gov/14676218/ DOI: 10.1074/jbc.m312719200
tissue_or_cell_type
Glutathionylated substrates
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 814–825
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human glutaredoxin kinetics and mutants · source_derived_draft · unverified_draft
### glutathione-glrx2-deglutathionylation GLRX2 reduced glutathionylated substrates with lower rate but higher affinity than GLRX1, giving similar catalytic efficiency. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione attached to a protein can be removed enzymatically. organism: Human GLRX1/GLRX2 tissue_or_cell_type: Glutathionylated substrates experimental_model: Purified human glutaredoxin kinetics and mutants limitations: Biochemical electron-donor alternatives; no claim that all cellular GLRX2 uses one route. exposure: GSH or NADPH/thioredoxin-reductase donor systems evidence_span: {"source_cache": "artifacts/glutathione-research/14676218.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a7399b7d035bd3815c30362449b7986dea08873c824e05506d7db627a71daa84", "start_char": 0, "end_char": 1398, "text_sha256": "a7399b7d035bd3815c30362449b7986dea08873c824e05506d7db627a71daa84"} [glutathione-p14676218] Human mitochondrial glutaredoxin reduces S-glutathionylated proteins with high affinity accepting electrons from either glutathione or thioredoxin reductase. (2004). https://pubmed.ncbi.nlm.nih.gov/14676218/ DOI: 10.1074/jbc.m312719200
Complete structured claim and evidence
A thioredoxin-reductase/NADPH system reduced GLRX2 disulfide and GSH-GLRX2 intermediates.
NADPH → Human glutaredoxin 2 / GLRX2 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/14676218.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a7399b7d035bd3815c30362449b7986dea08873c824e05506d7db627a71daa84", "start_char": 0, "end_char": 1398, "text_sha256": "a7399b7d035bd3815c30362449b7986dea08873c824e05506d7db627a71daa84"}
experimental_model
Purified human glutaredoxin kinetics and mutants
exposure
GSH or NADPH/thioredoxin-reductase donor systems
limitations
Thioredoxin-reductase isoform is not assigned from the indexed abstract; this is not a new selenium-dose response.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human GLRX1/GLRX2
plain_language
Glutaredoxin recovery also had an alternative donor route in the assay.
primary_references
[glutathione-p14676218] Human mitochondrial glutaredoxin reduces S-glutathionylated proteins with high affinity accepting electrons from either glutathione or thioredoxin reductase. (2004). https://pubmed.ncbi.nlm.nih.gov/14676218/ DOI: 10.1074/jbc.m312719200
tissue_or_cell_type
Glutathionylated substrates
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 827–838
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human glutaredoxin kinetics and mutants · source_derived_draft · unverified_draft
### glutathione-glrx2-alternative-donor A thioredoxin-reductase/NADPH system reduced GLRX2 disulfide and GSH-GLRX2 intermediates. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutaredoxin recovery also had an alternative donor route in the assay. organism: Human GLRX1/GLRX2 tissue_or_cell_type: Glutathionylated substrates experimental_model: Purified human glutaredoxin kinetics and mutants limitations: Thioredoxin-reductase isoform is not assigned from the indexed abstract; this is not a new selenium-dose response. exposure: GSH or NADPH/thioredoxin-reductase donor systems evidence_span: {"source_cache": "artifacts/glutathione-research/14676218.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a7399b7d035bd3815c30362449b7986dea08873c824e05506d7db627a71daa84", "start_char": 0, "end_char": 1398, "text_sha256": "a7399b7d035bd3815c30362449b7986dea08873c824e05506d7db627a71daa84"} [glutathione-p14676218] Human mitochondrial glutaredoxin reduces S-glutathionylated proteins with high affinity accepting electrons from either glutathione or thioredoxin reductase. (2004). https://pubmed.ncbi.nlm.nih.gov/14676218/ DOI: 10.1074/jbc.m312719200
Complete structured claim and evidence
GAPDH S-glutathionylation did not itself inactivate the enzyme in this assay.
S-Glutathionylation of purified human GAPDH → Purified human GAPDH catalytic activity source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/9642155.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "701b6cbdc44486c0b9423d7c30f52b282f1407958c7dde45d4aa1d3751718a72", "start_char": 0, "end_char": 1538, "text_sha256": "701b6cbdc44486c0b9423d7c30f52b282f1407958c7dde45d4aa1d3751718a72"}
experimental_model
Purified GAPDH oxidation and radiolabeled disulfide assays
exposure
Hydrogen peroxide versus GSSG and glutaredoxin
limitations
This particular assay separates oxidation from glutathionylation; it does not establish one universal effect for all modified proteins.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human GAPDH; human or bacterial glutaredoxin
plain_language
A glutathione tag is not automatically a protein-off switch.
primary_references
[glutathione-p9642155] Studies on the mechanism of oxidative modification of human glyceraldehyde-3-phosphate dehydrogenase by glutathione: catalysis by glutaredoxin. (1998). https://pubmed.ncbi.nlm.nih.gov/9642155/ DOI: 10.1006/bbrc.1998.8695
tissue_or_cell_type
Cell-free enzyme system
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 840–851
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified GAPDH oxidation and radiolabeled disulfide assays · source_derived_draft · unverified_draft
### glutathione-gapdh-glutathionylation-null GAPDH S-glutathionylation did not itself inactivate the enzyme in this assay. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: A glutathione tag is not automatically a protein-off switch. organism: Human GAPDH; human or bacterial glutaredoxin tissue_or_cell_type: Cell-free enzyme system experimental_model: Purified GAPDH oxidation and radiolabeled disulfide assays limitations: This particular assay separates oxidation from glutathionylation; it does not establish one universal effect for all modified proteins. exposure: Hydrogen peroxide versus GSSG and glutaredoxin evidence_span: {"source_cache": "artifacts/glutathione-research/9642155.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "701b6cbdc44486c0b9423d7c30f52b282f1407958c7dde45d4aa1d3751718a72", "start_char": 0, "end_char": 1538, "text_sha256": "701b6cbdc44486c0b9423d7c30f52b282f1407958c7dde45d4aa1d3751718a72"} [glutathione-p9642155] Studies on the mechanism of oxidative modification of human glyceraldehyde-3-phosphate dehydrogenase by glutathione: catalysis by glutaredoxin. (1998). https://pubmed.ncbi.nlm.nih.gov/9642155/ DOI: 10.1006/bbrc.1998.8695
Complete structured claim and evidence
Direct hydrogen-peroxide oxidation inhibited GAPDH activity in the comparison.
Hydrogen peroxide → Purified human GAPDH catalytic activity source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/9642155.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "701b6cbdc44486c0b9423d7c30f52b282f1407958c7dde45d4aa1d3751718a72", "start_char": 0, "end_char": 1538, "text_sha256": "701b6cbdc44486c0b9423d7c30f52b282f1407958c7dde45d4aa1d3751718a72"}
experimental_model
Purified GAPDH oxidation and radiolabeled disulfide assays
exposure
Hydrogen peroxide versus GSSG and glutaredoxin
limitations
This particular assay separates oxidation from glutathionylation; it does not establish one universal effect for all modified proteins.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human GAPDH; human or bacterial glutaredoxin
plain_language
The kind of chemical modification mattered.
primary_references
[glutathione-p9642155] Studies on the mechanism of oxidative modification of human glyceraldehyde-3-phosphate dehydrogenase by glutathione: catalysis by glutaredoxin. (1998). https://pubmed.ncbi.nlm.nih.gov/9642155/ DOI: 10.1006/bbrc.1998.8695
tissue_or_cell_type
Cell-free enzyme system
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 853–864
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified GAPDH oxidation and radiolabeled disulfide assays · source_derived_draft · unverified_draft
### glutathione-gapdh-peroxide Direct hydrogen-peroxide oxidation inhibited GAPDH activity in the comparison. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The kind of chemical modification mattered. organism: Human GAPDH; human or bacterial glutaredoxin tissue_or_cell_type: Cell-free enzyme system experimental_model: Purified GAPDH oxidation and radiolabeled disulfide assays limitations: This particular assay separates oxidation from glutathionylation; it does not establish one universal effect for all modified proteins. exposure: Hydrogen peroxide versus GSSG and glutaredoxin evidence_span: {"source_cache": "artifacts/glutathione-research/9642155.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "701b6cbdc44486c0b9423d7c30f52b282f1407958c7dde45d4aa1d3751718a72", "start_char": 0, "end_char": 1538, "text_sha256": "701b6cbdc44486c0b9423d7c30f52b282f1407958c7dde45d4aa1d3751718a72"} [glutathione-p9642155] Studies on the mechanism of oxidative modification of human glyceraldehyde-3-phosphate dehydrogenase by glutathione: catalysis by glutaredoxin. (1998). https://pubmed.ncbi.nlm.nih.gov/9642155/ DOI: 10.1006/bbrc.1998.8695
Complete structured claim and evidence
Recombinant human glutaredoxin enhanced GAPDH S-glutathionylation under the tested GSSG conditions.
Human glutaredoxin 1 / GLRX → S-Glutathionylation of purified human GAPDH source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/9642155.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "701b6cbdc44486c0b9423d7c30f52b282f1407958c7dde45d4aa1d3751718a72", "start_char": 0, "end_char": 1538, "text_sha256": "701b6cbdc44486c0b9423d7c30f52b282f1407958c7dde45d4aa1d3751718a72"}
experimental_model
Purified GAPDH oxidation and radiolabeled disulfide assays
exposure
Hydrogen peroxide versus GSSG and glutaredoxin
limitations
This particular assay separates oxidation from glutathionylation; it does not establish one universal effect for all modified proteins.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human GAPDH; human or bacterial glutaredoxin
plain_language
Reaction conditions can change the direction of a redox enzyme’s effect.
primary_references
[glutathione-p9642155] Studies on the mechanism of oxidative modification of human glyceraldehyde-3-phosphate dehydrogenase by glutathione: catalysis by glutaredoxin. (1998). https://pubmed.ncbi.nlm.nih.gov/9642155/ DOI: 10.1006/bbrc.1998.8695
tissue_or_cell_type
Cell-free enzyme system
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 866–877
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified GAPDH oxidation and radiolabeled disulfide assays · source_derived_draft · unverified_draft
### glutathione-glrx-gapdh-tagging Recombinant human glutaredoxin enhanced GAPDH S-glutathionylation under the tested GSSG conditions. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reaction conditions can change the direction of a redox enzyme’s effect. organism: Human GAPDH; human or bacterial glutaredoxin tissue_or_cell_type: Cell-free enzyme system experimental_model: Purified GAPDH oxidation and radiolabeled disulfide assays limitations: This particular assay separates oxidation from glutathionylation; it does not establish one universal effect for all modified proteins. exposure: Hydrogen peroxide versus GSSG and glutaredoxin evidence_span: {"source_cache": "artifacts/glutathione-research/9642155.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "701b6cbdc44486c0b9423d7c30f52b282f1407958c7dde45d4aa1d3751718a72", "start_char": 0, "end_char": 1538, "text_sha256": "701b6cbdc44486c0b9423d7c30f52b282f1407958c7dde45d4aa1d3751718a72"} [glutathione-p9642155] Studies on the mechanism of oxidative modification of human glyceraldehyde-3-phosphate dehydrogenase by glutathione: catalysis by glutaredoxin. (1998). https://pubmed.ncbi.nlm.nih.gov/9642155/ DOI: 10.1006/bbrc.1998.8695
Complete structured claim and evidence
Human GLO1 catalyzes glutathione-dependent methylglyoxal inactivation.
Human glyoxalase I / GLO1 → Methylglyoxal source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/9218781.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e00867a8f693a2a0e6506a87d162a52ce4aa75ac846c7b0495dcf6ad7c9330e1", "start_char": 0, "end_char": 1251, "text_sha256": "e00867a8f693a2a0e6506a87d162a52ce4aa75ac846c7b0495dcf6ad7c9330e1"}
experimental_model
Human GLO1 crystal structure
exposure
S-benzyl-GSH complex
limitations
The essential zinc site is biochemical evidence; neither zinc nor GSH supplementation was tested.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
Glutathione also participates in handling a reactive carbonyl compound.
primary_references
[glutathione-p9218781] Crystal structure of human glyoxalase I--evidence for gene duplication and 3D domain swapping. (1997). https://pubmed.ncbi.nlm.nih.gov/9218781/ DOI: 10.1093/emboj/16.12.3386
tissue_or_cell_type
Purified dimeric enzyme
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 879–890
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human GLO1 crystal structure · source_derived_draft · unverified_draft
### glutathione-glo1-methylglyoxal Human GLO1 catalyzes glutathione-dependent methylglyoxal inactivation. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione also participates in handling a reactive carbonyl compound. organism: Human tissue_or_cell_type: Purified dimeric enzyme experimental_model: Human GLO1 crystal structure limitations: The essential zinc site is biochemical evidence; neither zinc nor GSH supplementation was tested. exposure: S-benzyl-GSH complex evidence_span: {"source_cache": "artifacts/glutathione-research/9218781.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e00867a8f693a2a0e6506a87d162a52ce4aa75ac846c7b0495dcf6ad7c9330e1", "start_char": 0, "end_char": 1251, "text_sha256": "e00867a8f693a2a0e6506a87d162a52ce4aa75ac846c7b0495dcf6ad7c9330e1"} [glutathione-p9218781] Crystal structure of human glyoxalase I--evidence for gene duplication and 3D domain swapping. (1997). https://pubmed.ncbi.nlm.nih.gov/9218781/ DOI: 10.1093/emboj/16.12.3386
Complete structured claim and evidence
The human GLO1 active site contained an essential zinc ion with ligands contributed across the dimer interface.
Zinc(II) ion → Human glyoxalase I / GLO1 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/9218781.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e00867a8f693a2a0e6506a87d162a52ce4aa75ac846c7b0495dcf6ad7c9330e1", "start_char": 0, "end_char": 1251, "text_sha256": "e00867a8f693a2a0e6506a87d162a52ce4aa75ac846c7b0495dcf6ad7c9330e1"}
experimental_model
Human GLO1 crystal structure
exposure
S-benzyl-GSH complex
limitations
The essential zinc site is biochemical evidence; neither zinc nor GSH supplementation was tested.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
Zinc-dependent enzyme machinery connects to this glutathione pathway.
primary_references
[glutathione-p9218781] Crystal structure of human glyoxalase I--evidence for gene duplication and 3D domain swapping. (1997). https://pubmed.ncbi.nlm.nih.gov/9218781/ DOI: 10.1093/emboj/16.12.3386
tissue_or_cell_type
Purified dimeric enzyme
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 892–903
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human GLO1 crystal structure · source_derived_draft · unverified_draft
### glutathione-glo1-zinc The human GLO1 active site contained an essential zinc ion with ligands contributed across the dimer interface. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Zinc-dependent enzyme machinery connects to this glutathione pathway. organism: Human tissue_or_cell_type: Purified dimeric enzyme experimental_model: Human GLO1 crystal structure limitations: The essential zinc site is biochemical evidence; neither zinc nor GSH supplementation was tested. exposure: S-benzyl-GSH complex evidence_span: {"source_cache": "artifacts/glutathione-research/9218781.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "e00867a8f693a2a0e6506a87d162a52ce4aa75ac846c7b0495dcf6ad7c9330e1", "start_char": 0, "end_char": 1251, "text_sha256": "e00867a8f693a2a0e6506a87d162a52ce4aa75ac846c7b0495dcf6ad7c9330e1"} [glutathione-p9218781] Crystal structure of human glyoxalase I--evidence for gene duplication and 3D domain swapping. (1997). https://pubmed.ncbi.nlm.nih.gov/9218781/ DOI: 10.1093/emboj/16.12.3386
Complete structured claim and evidence
Human glyoxalase II hydrolyzes S-D-lactoylglutathione to GSH and D-lactate.
Human glyoxalase II / HAGH → S-D-Lactoylglutathione source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/10508780.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2a3bc96920fd7c09bc46bfbdd6ade9698bb3dd421e0867023dec7679628d04eb", "start_char": 0, "end_char": 1432, "text_sha256": "2a3bc96920fd7c09bc46bfbdd6ade9698bb3dd421e0867023dec7679628d04eb"}
experimental_model
Crystal structures of free and ligand-bound GLO2
exposure
Thioester hydrolysis and substrate-analogue structure
limitations
The structure contained a binuclear zinc site; metal occupancy in this preparation is not a universal in-vivo metal assignment.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
This clearance route regenerates glutathione instead of permanently consuming it.
primary_references
[glutathione-p10508780] Crystal structure of human glyoxalase II and its complex with a glutathione thiolester substrate analogue. (1999). https://pubmed.ncbi.nlm.nih.gov/10508780/ DOI: 10.1016/s0969-2126(99)80174-9
tissue_or_cell_type
Purified glyoxalase II
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 905–916
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Crystal structures of free and ligand-bound GLO2 · source_derived_draft · unverified_draft
### glutathione-glo2-recycles Human glyoxalase II hydrolyzes S-D-lactoylglutathione to GSH and D-lactate. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: This clearance route regenerates glutathione instead of permanently consuming it. organism: Human tissue_or_cell_type: Purified glyoxalase II experimental_model: Crystal structures of free and ligand-bound GLO2 limitations: The structure contained a binuclear zinc site; metal occupancy in this preparation is not a universal in-vivo metal assignment. exposure: Thioester hydrolysis and substrate-analogue structure evidence_span: {"source_cache": "artifacts/glutathione-research/10508780.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2a3bc96920fd7c09bc46bfbdd6ade9698bb3dd421e0867023dec7679628d04eb", "start_char": 0, "end_char": 1432, "text_sha256": "2a3bc96920fd7c09bc46bfbdd6ade9698bb3dd421e0867023dec7679628d04eb"} [glutathione-p10508780] Crystal structure of human glyoxalase II and its complex with a glutathione thiolester substrate analogue. (1999). https://pubmed.ncbi.nlm.nih.gov/10508780/ DOI: 10.1016/s0969-2126(99)80174-9
Complete structured claim and evidence
Human erythrocyte GLO1 forms S-D-lactoylglutathione through the methylglyoxal/GSH hemithioacetal intermediate.
Human glyoxalase I / GLO1 → Methylglyoxal-glutathione hemithioacetal source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/6863314.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fc40fe8d31ed36ad75af255cf31121d46ab8905d456f4ff9d94cc857e6b0e00d", "start_char": 0, "end_char": 2097, "text_sha256": "fc40fe8d31ed36ad75af255cf31121d46ab8905d456f4ff9d94cc857e6b0e00d"}
experimental_model
Forward/reverse enzyme kinetics
exposure
Lactoyl-GSH and thiol-trapping experiments
limitations
Artificial trapping reveals reversibility; it does not reverse the usual physiological net flux.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human erythrocyte enzyme; separate yeast comparison
plain_language
The first enzyme supplies the substrate processed by glyoxalase II.
primary_references
[glutathione-p6863314] Reversal of the reaction catalyzed by glyoxalase I. Calculation of the equilibrium constant for the enzymatic reaction. (1983). https://pubmed.ncbi.nlm.nih.gov/6863314/ DOI: 10.1016/s0021-9258(18)32137-9
tissue_or_cell_type
Purified glyoxalase I
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 918–929
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Forward/reverse enzyme kinetics · source_derived_draft · unverified_draft
### glutathione-glo1-product Human erythrocyte GLO1 forms S-D-lactoylglutathione through the methylglyoxal/GSH hemithioacetal intermediate. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The first enzyme supplies the substrate processed by glyoxalase II. organism: Human erythrocyte enzyme; separate yeast comparison tissue_or_cell_type: Purified glyoxalase I experimental_model: Forward/reverse enzyme kinetics limitations: Artificial trapping reveals reversibility; it does not reverse the usual physiological net flux. exposure: Lactoyl-GSH and thiol-trapping experiments evidence_span: {"source_cache": "artifacts/glutathione-research/6863314.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "fc40fe8d31ed36ad75af255cf31121d46ab8905d456f4ff9d94cc857e6b0e00d", "start_char": 0, "end_char": 2097, "text_sha256": "fc40fe8d31ed36ad75af255cf31121d46ab8905d456f4ff9d94cc857e6b0e00d"} [glutathione-p6863314] Reversal of the reaction catalyzed by glyoxalase I. Calculation of the equilibrium constant for the enzymatic reaction. (1983). https://pubmed.ncbi.nlm.nih.gov/6863314/ DOI: 10.1016/s0021-9258(18)32137-9
Complete structured claim and evidence
Human LTC4S conjugates GSH with leukotriene A4 to make leukotriene C4.
Human leukotriene C4 synthase / LTC4S → Leukotriene C4 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/20980252.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5eacc338c23e1f1be126ba80eebc8ac0ce7ea8735f22a5583dcebd7ef44eded4", "start_char": 0, "end_char": 1776, "text_sha256": "5eacc338c23e1f1be126ba80eebc8ac0ce7ea8735f22a5583dcebd7ef44eded4"}
experimental_model
LTC4S mutagenesis, spectroscopy and crystallography
exposure
Arg104 and Arg31 substitutions
limitations
GSH participates in inflammatory mediator synthesis; biochemical use does not imply that GSH supplements cause asthma.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
Glutathione is also a building block for a signaling molecule.
primary_references
[glutathione-p20980252] Arginine 104 is a key catalytic residue in leukotriene C4 synthase. (2010). https://pubmed.ncbi.nlm.nih.gov/20980252/ DOI: 10.1074/jbc.m110.105940
tissue_or_cell_type
Purified membrane enzyme
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 931–942
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · LTC4S mutagenesis, spectroscopy and crystallography · source_derived_draft · unverified_draft
### glutathione-ltc4s-product Human LTC4S conjugates GSH with leukotriene A4 to make leukotriene C4. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione is also a building block for a signaling molecule. organism: Human tissue_or_cell_type: Purified membrane enzyme experimental_model: LTC4S mutagenesis, spectroscopy and crystallography limitations: GSH participates in inflammatory mediator synthesis; biochemical use does not imply that GSH supplements cause asthma. exposure: Arg104 and Arg31 substitutions evidence_span: {"source_cache": "artifacts/glutathione-research/20980252.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5eacc338c23e1f1be126ba80eebc8ac0ce7ea8735f22a5583dcebd7ef44eded4", "start_char": 0, "end_char": 1776, "text_sha256": "5eacc338c23e1f1be126ba80eebc8ac0ce7ea8735f22a5583dcebd7ef44eded4"} [glutathione-p20980252] Arginine 104 is a key catalytic residue in leukotriene C4 synthase. (2010). https://pubmed.ncbi.nlm.nih.gov/20980252/ DOI: 10.1074/jbc.m110.105940
Complete structured claim and evidence
Arg104 substitutions abolished 94.3–99.9% of LTC4S specific activity; selected variants lacked the GSH thiolate signal.
Human LTC4S Arg104Ala/Ser/Thr/Lys variants → Human leukotriene C4 synthase / LTC4S source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/20980252.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5eacc338c23e1f1be126ba80eebc8ac0ce7ea8735f22a5583dcebd7ef44eded4", "start_char": 0, "end_char": 1776, "text_sha256": "5eacc338c23e1f1be126ba80eebc8ac0ce7ea8735f22a5583dcebd7ef44eded4"}
experimental_model
LTC4S mutagenesis, spectroscopy and crystallography
exposure
Arg104 and Arg31 substitutions
limitations
GSH participates in inflammatory mediator synthesis; biochemical use does not imply that GSH supplements cause asthma.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
The enzyme activates the glutathione sulfur for conjugation.
primary_references
[glutathione-p20980252] Arginine 104 is a key catalytic residue in leukotriene C4 synthase. (2010). https://pubmed.ncbi.nlm.nih.gov/20980252/ DOI: 10.1074/jbc.m110.105940
tissue_or_cell_type
Purified membrane enzyme
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 944–955
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · LTC4S mutagenesis, spectroscopy and crystallography · source_derived_draft · unverified_draft
### glutathione-ltc4s-r104 Arg104 substitutions abolished 94.3–99.9% of LTC4S specific activity; selected variants lacked the GSH thiolate signal. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme activates the glutathione sulfur for conjugation. organism: Human tissue_or_cell_type: Purified membrane enzyme experimental_model: LTC4S mutagenesis, spectroscopy and crystallography limitations: GSH participates in inflammatory mediator synthesis; biochemical use does not imply that GSH supplements cause asthma. exposure: Arg104 and Arg31 substitutions evidence_span: {"source_cache": "artifacts/glutathione-research/20980252.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5eacc338c23e1f1be126ba80eebc8ac0ce7ea8735f22a5583dcebd7ef44eded4", "start_char": 0, "end_char": 1776, "text_sha256": "5eacc338c23e1f1be126ba80eebc8ac0ce7ea8735f22a5583dcebd7ef44eded4"} [glutathione-p20980252] Arginine 104 is a key catalytic residue in leukotriene C4 synthase. (2010). https://pubmed.ncbi.nlm.nih.gov/20980252/ DOI: 10.1074/jbc.m110.105940
Complete structured claim and evidence
PRDX6 heterodimerization with piGST supports glutathionylation needed in the peroxidatic cycle.
Human glutathione S-transferase P1 / GSTP1 → Human peroxiredoxin 6 / PRDX6 source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/26891882.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "919a342fc31314fef155eba006fd5a61b2a0a2d93a02c4de5e122c3d25d690fc", "start_char": 0, "end_char": 1661, "text_sha256": "919a342fc31314fef155eba006fd5a61b2a0a2d93a02c4de5e122c3d25d690fc"}
experimental_model
Human PRDX6 structures, dimerization and mutagenesis
exposure
Leu145/Leu148 substitutions
limitations
PRDX6 peroxidase and phospholipase activities are distinct; this is not a clinical GSTP1-variant study.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
A glutathione transferase helps reactivate another peroxide-handling enzyme.
primary_references
[glutathione-p26891882] Peroxiredoxin 6 homodimerization and heterodimerization with glutathione S-transferase pi are required for its peroxidase but not phospholipase A2 activity. (2016). https://pubmed.ncbi.nlm.nih.gov/26891882/ DOI: 10.1016/j.freeradbiomed.2016.02.012
tissue_or_cell_type
Purified protein and proximity assays
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 957–968
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human PRDX6 structures, dimerization and mutagenesis · source_derived_draft · unverified_draft
### glutathione-prdx6-gstp PRDX6 heterodimerization with piGST supports glutathionylation needed in the peroxidatic cycle. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: A glutathione transferase helps reactivate another peroxide-handling enzyme. organism: Human tissue_or_cell_type: Purified protein and proximity assays experimental_model: Human PRDX6 structures, dimerization and mutagenesis limitations: PRDX6 peroxidase and phospholipase activities are distinct; this is not a clinical GSTP1-variant study. exposure: Leu145/Leu148 substitutions evidence_span: {"source_cache": "artifacts/glutathione-research/26891882.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "919a342fc31314fef155eba006fd5a61b2a0a2d93a02c4de5e122c3d25d690fc", "start_char": 0, "end_char": 1661, "text_sha256": "919a342fc31314fef155eba006fd5a61b2a0a2d93a02c4de5e122c3d25d690fc"} [glutathione-p26891882] Peroxiredoxin 6 homodimerization and heterodimerization with glutathione S-transferase pi are required for its peroxidase but not phospholipase A2 activity. (2016). https://pubmed.ncbi.nlm.nih.gov/26891882/ DOI: 10.1016/j.freeradbiomed.2016.02.012
Complete structured claim and evidence
The double interface mutation essentially abolished PRDX6 peroxidase activity.
Human PRDX6 Leu145Glu/Leu148Glu double variant → Human PRDX6 peroxidase activity source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/26891882.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "919a342fc31314fef155eba006fd5a61b2a0a2d93a02c4de5e122c3d25d690fc", "start_char": 0, "end_char": 1661, "text_sha256": "919a342fc31314fef155eba006fd5a61b2a0a2d93a02c4de5e122c3d25d690fc"}
experimental_model
Human PRDX6 structures, dimerization and mutagenesis
exposure
Leu145/Leu148 substitutions
limitations
PRDX6 peroxidase and phospholipase activities are distinct; this is not a clinical GSTP1-variant study.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
Disrupting protein association interrupted the peroxide-handling function.
primary_references
[glutathione-p26891882] Peroxiredoxin 6 homodimerization and heterodimerization with glutathione S-transferase pi are required for its peroxidase but not phospholipase A2 activity. (2016). https://pubmed.ncbi.nlm.nih.gov/26891882/ DOI: 10.1016/j.freeradbiomed.2016.02.012
tissue_or_cell_type
Purified protein and proximity assays
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 970–981
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human PRDX6 structures, dimerization and mutagenesis · source_derived_draft · unverified_draft
### glutathione-prdx6-mutant-peroxidase The double interface mutation essentially abolished PRDX6 peroxidase activity. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Disrupting protein association interrupted the peroxide-handling function. organism: Human tissue_or_cell_type: Purified protein and proximity assays experimental_model: Human PRDX6 structures, dimerization and mutagenesis limitations: PRDX6 peroxidase and phospholipase activities are distinct; this is not a clinical GSTP1-variant study. exposure: Leu145/Leu148 substitutions evidence_span: {"source_cache": "artifacts/glutathione-research/26891882.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "919a342fc31314fef155eba006fd5a61b2a0a2d93a02c4de5e122c3d25d690fc", "start_char": 0, "end_char": 1661, "text_sha256": "919a342fc31314fef155eba006fd5a61b2a0a2d93a02c4de5e122c3d25d690fc"} [glutathione-p26891882] Peroxiredoxin 6 homodimerization and heterodimerization with glutathione S-transferase pi are required for its peroxidase but not phospholipase A2 activity. (2016). https://pubmed.ncbi.nlm.nih.gov/26891882/ DOI: 10.1016/j.freeradbiomed.2016.02.012
Complete structured claim and evidence
The same double mutation left phospholipase A2 activity unaffected.
Human PRDX6 Leu145Glu/Leu148Glu double variant → Human PRDX6 phospholipase A2 activity source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/26891882.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "919a342fc31314fef155eba006fd5a61b2a0a2d93a02c4de5e122c3d25d690fc", "start_char": 0, "end_char": 1661, "text_sha256": "919a342fc31314fef155eba006fd5a61b2a0a2d93a02c4de5e122c3d25d690fc"}
experimental_model
Human PRDX6 structures, dimerization and mutagenesis
exposure
Leu145/Leu148 substitutions
limitations
PRDX6 peroxidase and phospholipase activities are distinct; this is not a clinical GSTP1-variant study.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
One protein’s functions can fail independently.
primary_references
[glutathione-p26891882] Peroxiredoxin 6 homodimerization and heterodimerization with glutathione S-transferase pi are required for its peroxidase but not phospholipase A2 activity. (2016). https://pubmed.ncbi.nlm.nih.gov/26891882/ DOI: 10.1016/j.freeradbiomed.2016.02.012
tissue_or_cell_type
Purified protein and proximity assays
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 983–994
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human PRDX6 structures, dimerization and mutagenesis · source_derived_draft · unverified_draft
### glutathione-prdx6-mutant-pla2 The same double mutation left phospholipase A2 activity unaffected. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: One protein’s functions can fail independently. organism: Human tissue_or_cell_type: Purified protein and proximity assays experimental_model: Human PRDX6 structures, dimerization and mutagenesis limitations: PRDX6 peroxidase and phospholipase activities are distinct; this is not a clinical GSTP1-variant study. exposure: Leu145/Leu148 substitutions evidence_span: {"source_cache": "artifacts/glutathione-research/26891882.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "919a342fc31314fef155eba006fd5a61b2a0a2d93a02c4de5e122c3d25d690fc", "start_char": 0, "end_char": 1661, "text_sha256": "919a342fc31314fef155eba006fd5a61b2a0a2d93a02c4de5e122c3d25d690fc"} [glutathione-p26891882] Peroxiredoxin 6 homodimerization and heterodimerization with glutathione S-transferase pi are required for its peroxidase but not phospholipase A2 activity. (2016). https://pubmed.ncbi.nlm.nih.gov/26891882/ DOI: 10.1016/j.freeradbiomed.2016.02.012
Complete structured claim and evidence
The activity purified from mouse macrophages metabolized GSNO and was identified as glutathione-dependent formaldehyde dehydrogenase.
Mouse S-nitrosoglutathione reductase / Adh5 → S-Nitrosoglutathione / GSNO source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/11260719.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "37ea7e3741c139cea0718d0cdf5e81da638a0f67269277289aa3f715e4c5df61", "start_char": 0, "end_char": 1177, "text_sha256": "37ea7e3741c139cea0718d0cdf5e81da638a0f67269277289aa3f715e4c5df61"}
experimental_model
Purification and genetic deletion
exposure
GSNO-consuming enzyme identification and deletion
limitations
The mouse gene is kept separate from human ADH5. Protein SNO regulation is not identical to direct peroxide removal.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Bacteria, yeast and mouse; mouse findings separated
plain_language
A glutathione derivative links to nitric-oxide-related signaling.
primary_references
[glutathione-p11260719] A metabolic enzyme for S-nitrosothiol conserved from bacteria to humans. (2001). https://pubmed.ncbi.nlm.nih.gov/11260719/ DOI: 10.1038/35068596
tissue_or_cell_type
Cellular nitrosothiol metabolism
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 996–1007
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purification and genetic deletion · source_derived_draft · unverified_draft
### glutathione-gsnor-gsno The activity purified from mouse macrophages metabolized GSNO and was identified as glutathione-dependent formaldehyde dehydrogenase. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: A glutathione derivative links to nitric-oxide-related signaling. organism: Bacteria, yeast and mouse; mouse findings separated tissue_or_cell_type: Cellular nitrosothiol metabolism experimental_model: Purification and genetic deletion limitations: The mouse gene is kept separate from human ADH5. Protein SNO regulation is not identical to direct peroxide removal. exposure: GSNO-consuming enzyme identification and deletion evidence_span: {"source_cache": "artifacts/glutathione-research/11260719.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "37ea7e3741c139cea0718d0cdf5e81da638a0f67269277289aa3f715e4c5df61", "start_char": 0, "end_char": 1177, "text_sha256": "37ea7e3741c139cea0718d0cdf5e81da638a0f67269277289aa3f715e4c5df61"} [glutathione-p11260719] A metabolic enzyme for S-nitrosothiol conserved from bacteria to humans. (2001). https://pubmed.ncbi.nlm.nih.gov/11260719/ DOI: 10.1038/35068596
Complete structured claim and evidence
Reductase deletion increased protein SNO as well as GSNO in the studied mouse system.
Adh5-null mouse cells in the 2001 study → Mouse intracellular protein S-nitrosylation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/glutathione-research/11260719.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "37ea7e3741c139cea0718d0cdf5e81da638a0f67269277289aa3f715e4c5df61", "start_char": 0, "end_char": 1177, "text_sha256": "37ea7e3741c139cea0718d0cdf5e81da638a0f67269277289aa3f715e4c5df61"}
experimental_model
Purification and genetic deletion
exposure
GSNO-consuming enzyme identification and deletion
limitations
The mouse gene is kept separate from human ADH5. Protein SNO regulation is not identical to direct peroxide removal.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Bacteria, yeast and mouse; mouse findings separated
plain_language
Changing the small-molecule pool affected protein modifications.
primary_references
[glutathione-p11260719] A metabolic enzyme for S-nitrosothiol conserved from bacteria to humans. (2001). https://pubmed.ncbi.nlm.nih.gov/11260719/ DOI: 10.1038/35068596
tissue_or_cell_type
Cellular nitrosothiol metabolism
trigger_kind
machinery_impairment Imported condition classification; unverified.
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1009–1020
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purification and genetic deletion · source_derived_draft · unverified_draft
### glutathione-gsnor-protein-sno Reductase deletion increased protein SNO as well as GSNO in the studied mouse system. Condition category: machinery_impairment nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Changing the small-molecule pool affected protein modifications. organism: Bacteria, yeast and mouse; mouse findings separated tissue_or_cell_type: Cellular nitrosothiol metabolism experimental_model: Purification and genetic deletion limitations: The mouse gene is kept separate from human ADH5. Protein SNO regulation is not identical to direct peroxide removal. exposure: GSNO-consuming enzyme identification and deletion evidence_span: {"source_cache": "artifacts/glutathione-research/11260719.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "37ea7e3741c139cea0718d0cdf5e81da638a0f67269277289aa3f715e4c5df61", "start_char": 0, "end_char": 1177, "text_sha256": "37ea7e3741c139cea0718d0cdf5e81da638a0f67269277289aa3f715e4c5df61"} [glutathione-p11260719] A metabolic enzyme for S-nitrosothiol conserved from bacteria to humans. (2001). https://pubmed.ncbi.nlm.nih.gov/11260719/ DOI: 10.1038/35068596
Complete structured claim and evidence
Human liver enzyme kinetics supported NAD+-dependent processing of S-hydroxymethylglutathione to the S-formylglutathione/NADH products.
Human glutathione-dependent formaldehyde dehydrogenase / ADH5 → S-Hydroxymethylglutathione source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/7213635.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dd4cd3715345eebe37dce2f19274529ae09d9c0e5523348eb8fc9b57e854cfa5", "start_char": 0, "end_char": 592, "text_sha256": "dd4cd3715345eebe37dce2f19274529ae09d9c0e5523348eb8fc9b57e854cfa5"}
experimental_model
Product-inhibition kinetics
exposure
Forward and reverse reaction products
limitations
Kinetic mechanism; no evidence here for a dietary detoxification protocol.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
Glutathione carries formaldehyde through an enzyme-dependent route.
primary_references
[glutathione-p7213635] Product inhibition studies of human liver formaldehyde dehydrogenase. (1980). https://pubmed.ncbi.nlm.nih.gov/7213635/ DOI: 10.1016/0005-2744(80)90133-3
tissue_or_cell_type
Liver formaldehyde dehydrogenase
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1022–1033
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Product-inhibition kinetics · source_derived_draft · unverified_draft
### glutathione-adh5-formaldehyde Human liver enzyme kinetics supported NAD+-dependent processing of S-hydroxymethylglutathione to the S-formylglutathione/NADH products. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione carries formaldehyde through an enzyme-dependent route. organism: Human tissue_or_cell_type: Liver formaldehyde dehydrogenase experimental_model: Product-inhibition kinetics limitations: Kinetic mechanism; no evidence here for a dietary detoxification protocol. exposure: Forward and reverse reaction products evidence_span: {"source_cache": "artifacts/glutathione-research/7213635.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "dd4cd3715345eebe37dce2f19274529ae09d9c0e5523348eb8fc9b57e854cfa5", "start_char": 0, "end_char": 592, "text_sha256": "dd4cd3715345eebe37dce2f19274529ae09d9c0e5523348eb8fc9b57e854cfa5"} [glutathione-p7213635] Product inhibition studies of human liver formaldehyde dehydrogenase. (1980). https://pubmed.ncbi.nlm.nih.gov/7213635/ DOI: 10.1016/0005-2744(80)90133-3
Complete structured claim and evidence
Adding GSH decreased covalent microsomal protein binding while forming 3-S-glutathionylacetaminophen.
GSH → N-Acetyl-p-benzoquinone imine / NAPQI source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/6424115.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8c45563e89388d200eb64ae63d12b388ef5cca91369a585157ef27b39f525b08", "start_char": 0, "end_char": 1307, "text_sha256": "8c45563e89388d200eb64ae63d12b388ef5cca91369a585157ef27b39f525b08"}
experimental_model
Enzyme oxidation and radiolabeled binding assays
exposure
NAPQI or acetaminophen with reductants
limitations
Experimental chemistry; no new human dose threshold or treatment regimen is inferred.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Mouse microsomes and cell-free cytochrome-P450 system
plain_language
Glutathione diverted the reactive metabolite into a conjugate.
primary_references
[glutathione-p6424115] N-acetyl-p-benzoquinone imine: a cytochrome P-450-mediated oxidation product of acetaminophen. (1984). https://pubmed.ncbi.nlm.nih.gov/6424115/ DOI: 10.1073/pnas.81.5.1327
tissue_or_cell_type
Acetaminophen reactive-metabolite handling
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1035–1046
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Enzyme oxidation and radiolabeled binding assays · source_derived_draft · unverified_draft
### glutathione-napqi-conjugation Adding GSH decreased covalent microsomal protein binding while forming 3-S-glutathionylacetaminophen. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione diverted the reactive metabolite into a conjugate. organism: Mouse microsomes and cell-free cytochrome-P450 system tissue_or_cell_type: Acetaminophen reactive-metabolite handling experimental_model: Enzyme oxidation and radiolabeled binding assays limitations: Experimental chemistry; no new human dose threshold or treatment regimen is inferred. exposure: NAPQI or acetaminophen with reductants evidence_span: {"source_cache": "artifacts/glutathione-research/6424115.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8c45563e89388d200eb64ae63d12b388ef5cca91369a585157ef27b39f525b08", "start_char": 0, "end_char": 1307, "text_sha256": "8c45563e89388d200eb64ae63d12b388ef5cca91369a585157ef27b39f525b08"} [glutathione-p6424115] N-acetyl-p-benzoquinone imine: a cytochrome P-450-mediated oxidation product of acetaminophen. (1984). https://pubmed.ncbi.nlm.nih.gov/6424115/ DOI: 10.1073/pnas.81.5.1327
Complete structured claim and evidence
Cytochrome-P450-mediated acetaminophen oxidation produced NAPQI in the experimental oxidation system.
Paracetamol → N-Acetyl-p-benzoquinone imine / NAPQI source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/6424115.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8c45563e89388d200eb64ae63d12b388ef5cca91369a585157ef27b39f525b08", "start_char": 0, "end_char": 1307, "text_sha256": "8c45563e89388d200eb64ae63d12b388ef5cca91369a585157ef27b39f525b08"}
experimental_model
Enzyme oxidation and radiolabeled binding assays
exposure
NAPQI or acetaminophen with reductants
limitations
Experimental chemistry; no new human dose threshold or treatment regimen is inferred.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Mouse microsomes and cell-free cytochrome-P450 system
plain_language
The parent drug and its reactive metabolite are separate chemical entities.
primary_references
[glutathione-p6424115] N-acetyl-p-benzoquinone imine: a cytochrome P-450-mediated oxidation product of acetaminophen. (1984). https://pubmed.ncbi.nlm.nih.gov/6424115/ DOI: 10.1073/pnas.81.5.1327
tissue_or_cell_type
Acetaminophen reactive-metabolite handling
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1048–1059
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Enzyme oxidation and radiolabeled binding assays · source_derived_draft · unverified_draft
### glutathione-acetaminophen-napqi Cytochrome-P450-mediated acetaminophen oxidation produced NAPQI in the experimental oxidation system. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The parent drug and its reactive metabolite are separate chemical entities. organism: Mouse microsomes and cell-free cytochrome-P450 system tissue_or_cell_type: Acetaminophen reactive-metabolite handling experimental_model: Enzyme oxidation and radiolabeled binding assays limitations: Experimental chemistry; no new human dose threshold or treatment regimen is inferred. exposure: NAPQI or acetaminophen with reductants evidence_span: {"source_cache": "artifacts/glutathione-research/6424115.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8c45563e89388d200eb64ae63d12b388ef5cca91369a585157ef27b39f525b08", "start_char": 0, "end_char": 1307, "text_sha256": "8c45563e89388d200eb64ae63d12b388ef5cca91369a585157ef27b39f525b08"} [glutathione-p6424115] N-acetyl-p-benzoquinone imine: a cytochrome P-450-mediated oxidation product of acetaminophen. (1984). https://pubmed.ncbi.nlm.nih.gov/6424115/ DOI: 10.1073/pnas.81.5.1327
Complete structured claim and evidence
Ascorbic acid decreased binding through reduction of NAPQI to acetaminophen in the comparison.
L-Ascorbate → N-Acetyl-p-benzoquinone imine / NAPQI source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/6424115.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8c45563e89388d200eb64ae63d12b388ef5cca91369a585157ef27b39f525b08", "start_char": 0, "end_char": 1307, "text_sha256": "8c45563e89388d200eb64ae63d12b388ef5cca91369a585157ef27b39f525b08"}
experimental_model
Enzyme oxidation and radiolabeled binding assays
exposure
NAPQI or acetaminophen with reductants
limitations
Cell-free/microsomal finding; vitamin C is not established here as a clinical antidote.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Mouse microsomes and cell-free cytochrome-P450 system
plain_language
Different reductants changed the same reactive intermediate by different chemistry.
primary_references
[glutathione-p6424115] N-acetyl-p-benzoquinone imine: a cytochrome P-450-mediated oxidation product of acetaminophen. (1984). https://pubmed.ncbi.nlm.nih.gov/6424115/ DOI: 10.1073/pnas.81.5.1327
tissue_or_cell_type
Acetaminophen reactive-metabolite handling
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1061–1072
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Enzyme oxidation and radiolabeled binding assays · source_derived_draft · unverified_draft
### glutathione-napqi-ascorbate Ascorbic acid decreased binding through reduction of NAPQI to acetaminophen in the comparison. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Different reductants changed the same reactive intermediate by different chemistry. organism: Mouse microsomes and cell-free cytochrome-P450 system tissue_or_cell_type: Acetaminophen reactive-metabolite handling experimental_model: Enzyme oxidation and radiolabeled binding assays limitations: Cell-free/microsomal finding; vitamin C is not established here as a clinical antidote. exposure: NAPQI or acetaminophen with reductants evidence_span: {"source_cache": "artifacts/glutathione-research/6424115.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8c45563e89388d200eb64ae63d12b388ef5cca91369a585157ef27b39f525b08", "start_char": 0, "end_char": 1307, "text_sha256": "8c45563e89388d200eb64ae63d12b388ef5cca91369a585157ef27b39f525b08"} [glutathione-p6424115] N-acetyl-p-benzoquinone imine: a cytochrome P-450-mediated oxidation product of acetaminophen. (1984). https://pubmed.ncbi.nlm.nih.gov/6424115/ DOI: 10.1073/pnas.81.5.1327
Complete structured claim and evidence
Peptide mapping identified NAPQI binding to GSS Cys422.
N-Acetyl-p-benzoquinone imine / NAPQI → Human glutathione synthetase / GSS source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/glutathione-research/27086508.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3170945d1b6429e4d069dffe5fefd919b06714d7bea8a2b82d4b9eda916e9cad", "start_char": 0, "end_char": 1383, "text_sha256": "3170945d1b6429e4d069dffe5fefd919b06714d7bea8a2b82d4b9eda916e9cad"}
experimental_model
Mass spectrometry and in-vitro inhibition
exposure
0.77 micromolar enzyme with 25–400 micromolar NAPQI
limitations
Biological relevance and contribution to human 5-oxoprolinuric acidosis remain unproven.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human GSS preparation
plain_language
The reactive metabolite can attack synthesis machinery in vitro.
primary_references
[glutathione-p27086508] The acetaminophen metabolite N-acetyl-p-benzoquinone imine (NAPQI) inhibits glutathione synthetase in vitro; a clue to the mechanism of 5-oxoprolinuric acidosis? (2017). https://pubmed.ncbi.nlm.nih.gov/27086508/ DOI: 10.3109/00498254.2016.1166533
tissue_or_cell_type
Purified synthesis enzyme
trigger_kind
machinery_impairment Imported condition classification; unverified.
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1074–1085
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mass spectrometry and in-vitro inhibition · source_derived_draft · unverified_draft
### glutathione-napqi-gss-binding Peptide mapping identified NAPQI binding to GSS Cys422. Condition category: machinery_impairment nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The reactive metabolite can attack synthesis machinery in vitro. organism: Human GSS preparation tissue_or_cell_type: Purified synthesis enzyme experimental_model: Mass spectrometry and in-vitro inhibition limitations: Biological relevance and contribution to human 5-oxoprolinuric acidosis remain unproven. exposure: 0.77 micromolar enzyme with 25–400 micromolar NAPQI evidence_span: {"source_cache": "artifacts/glutathione-research/27086508.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3170945d1b6429e4d069dffe5fefd919b06714d7bea8a2b82d4b9eda916e9cad", "start_char": 0, "end_char": 1383, "text_sha256": "3170945d1b6429e4d069dffe5fefd919b06714d7bea8a2b82d4b9eda916e9cad"} [glutathione-p27086508] The acetaminophen metabolite N-acetyl-p-benzoquinone imine (NAPQI) inhibits glutathione synthetase in vitro; a clue to the mechanism of 5-oxoprolinuric acidosis? (2017). https://pubmed.ncbi.nlm.nih.gov/27086508/ DOI: 10.3109/00498254.2016.1166533
Complete structured claim and evidence
NAPQI at 25–400 micromolar irreversibly reduced measured GSS activity by 16–89%.
N-Acetyl-p-benzoquinone imine / NAPQI → Human glutathione synthetase catalytic activity source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/glutathione-research/27086508.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3170945d1b6429e4d069dffe5fefd919b06714d7bea8a2b82d4b9eda916e9cad", "start_char": 0, "end_char": 1383, "text_sha256": "3170945d1b6429e4d069dffe5fefd919b06714d7bea8a2b82d4b9eda916e9cad"}
experimental_model
Mass spectrometry and in-vitro inhibition
exposure
0.77 micromolar enzyme with 25–400 micromolar NAPQI
limitations
Biological relevance and contribution to human 5-oxoprolinuric acidosis remain unproven.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human GSS preparation
plain_language
The assay suggests a possible feedback problem: stress can impair replenishment.
primary_references
[glutathione-p27086508] The acetaminophen metabolite N-acetyl-p-benzoquinone imine (NAPQI) inhibits glutathione synthetase in vitro; a clue to the mechanism of 5-oxoprolinuric acidosis? (2017). https://pubmed.ncbi.nlm.nih.gov/27086508/ DOI: 10.3109/00498254.2016.1166533
tissue_or_cell_type
Purified synthesis enzyme
trigger_kind
machinery_impairment Imported condition classification; unverified.
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1087–1098
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mass spectrometry and in-vitro inhibition · source_derived_draft · unverified_draft
### glutathione-napqi-gss-inhibition NAPQI at 25–400 micromolar irreversibly reduced measured GSS activity by 16–89%. Condition category: machinery_impairment nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The assay suggests a possible feedback problem: stress can impair replenishment. organism: Human GSS preparation tissue_or_cell_type: Purified synthesis enzyme experimental_model: Mass spectrometry and in-vitro inhibition limitations: Biological relevance and contribution to human 5-oxoprolinuric acidosis remain unproven. exposure: 0.77 micromolar enzyme with 25–400 micromolar NAPQI evidence_span: {"source_cache": "artifacts/glutathione-research/27086508.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3170945d1b6429e4d069dffe5fefd919b06714d7bea8a2b82d4b9eda916e9cad", "start_char": 0, "end_char": 1383, "text_sha256": "3170945d1b6429e4d069dffe5fefd919b06714d7bea8a2b82d4b9eda916e9cad"} [glutathione-p27086508] The acetaminophen metabolite N-acetyl-p-benzoquinone imine (NAPQI) inhibits glutathione synthetase in vitro; a clue to the mechanism of 5-oxoprolinuric acidosis? (2017). https://pubmed.ncbi.nlm.nih.gov/27086508/ DOI: 10.3109/00498254.2016.1166533
Complete structured claim and evidence
After supplementation, older participants had a 78.8% higher fractional GSH synthesis rate.
Glycine plus cysteine-precursor supplementation in the 2011 tracer study → Human erythrocyte glutathione synthesis rate source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/glutathione-research/21795440.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd", "start_char": 0, "end_char": 2139, "text_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd"}
experimental_model
Stable-isotope tracer study with before/after supplementation
exposure
Two weeks of glycine/cysteine-precursor supplementation in older participants
limitations
Small non-placebo-controlled intervention; age comparison and treatment response are not universal aging rules.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
The fraction of the pool synthesized each day increased.
primary_references
[glutathione-p21795440] Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. (2011). https://pubmed.ncbi.nlm.nih.gov/21795440/ DOI: 10.3945/ajcn.110.003483
tissue_or_cell_type
Eight older and eight younger adults; erythrocytes
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1100–1111
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stable-isotope tracer study with before/after supplementation · source_derived_draft · unverified_draft
### glutathione-precursor-synthesis After supplementation, older participants had a 78.8% higher fractional GSH synthesis rate. Condition category: nutrient_deficiency nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The fraction of the pool synthesized each day increased. organism: Human tissue_or_cell_type: Eight older and eight younger adults; erythrocytes experimental_model: Stable-isotope tracer study with before/after supplementation limitations: Small non-placebo-controlled intervention; age comparison and treatment response are not universal aging rules. exposure: Two weeks of glycine/cysteine-precursor supplementation in older participants evidence_span: {"source_cache": "artifacts/glutathione-research/21795440.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd", "start_char": 0, "end_char": 2139, "text_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd"} [glutathione-p21795440] Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. (2011). https://pubmed.ncbi.nlm.nih.gov/21795440/ DOI: 10.3945/ajcn.110.003483
Complete structured claim and evidence
The absolute erythrocyte GSH synthesis rate increased 230.9% after supplementation.
Glycine plus cysteine-precursor supplementation in the 2011 tracer study → Human erythrocyte absolute glutathione synthesis rate source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/glutathione-research/21795440.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd", "start_char": 0, "end_char": 2139, "text_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd"}
experimental_model
Stable-isotope tracer study with before/after supplementation
exposure
Two weeks of glycine/cysteine-precursor supplementation in older participants
limitations
Small non-placebo-controlled intervention; age comparison and treatment response are not universal aging rules.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
The measured amount produced also increased.
primary_references
[glutathione-p21795440] Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. (2011). https://pubmed.ncbi.nlm.nih.gov/21795440/ DOI: 10.3945/ajcn.110.003483
tissue_or_cell_type
Eight older and eight younger adults; erythrocytes
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1113–1124
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stable-isotope tracer study with before/after supplementation · source_derived_draft · unverified_draft
### glutathione-precursor-absolute-synthesis The absolute erythrocyte GSH synthesis rate increased 230.9% after supplementation. Condition category: nutrient_deficiency nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The measured amount produced also increased. organism: Human tissue_or_cell_type: Eight older and eight younger adults; erythrocytes experimental_model: Stable-isotope tracer study with before/after supplementation limitations: Small non-placebo-controlled intervention; age comparison and treatment response are not universal aging rules. exposure: Two weeks of glycine/cysteine-precursor supplementation in older participants evidence_span: {"source_cache": "artifacts/glutathione-research/21795440.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd", "start_char": 0, "end_char": 2139, "text_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd"} [glutathione-p21795440] Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. (2011). https://pubmed.ncbi.nlm.nih.gov/21795440/ DOI: 10.3945/ajcn.110.003483
Complete structured claim and evidence
The older group’s erythrocyte GSH concentration increased 94.6% after supplementation.
Glycine plus cysteine-precursor supplementation in the 2011 tracer study → Human erythrocyte glutathione concentration, study-defined assay pool source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/glutathione-research/21795440.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd", "start_char": 0, "end_char": 2139, "text_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd"}
experimental_model
Stable-isotope tracer study with before/after supplementation
exposure
Two weeks of glycine/cysteine-precursor supplementation in older participants
limitations
Small non-placebo-controlled intervention; age comparison and treatment response are not universal aging rules.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
A low measured pool increased in this small study.
primary_references
[glutathione-p21795440] Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. (2011). https://pubmed.ncbi.nlm.nih.gov/21795440/ DOI: 10.3945/ajcn.110.003483
tissue_or_cell_type
Eight older and eight younger adults; erythrocytes
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1126–1137
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Stable-isotope tracer study with before/after supplementation · source_derived_draft · unverified_draft
### glutathione-precursor-pool The older group’s erythrocyte GSH concentration increased 94.6% after supplementation. Condition category: nutrient_deficiency nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: A low measured pool increased in this small study. organism: Human tissue_or_cell_type: Eight older and eight younger adults; erythrocytes experimental_model: Stable-isotope tracer study with before/after supplementation limitations: Small non-placebo-controlled intervention; age comparison and treatment response are not universal aging rules. exposure: Two weeks of glycine/cysteine-precursor supplementation in older participants evidence_span: {"source_cache": "artifacts/glutathione-research/21795440.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd", "start_char": 0, "end_char": 2139, "text_sha256": "97479748f2fecc462981498968c43dd6199dcdb9c7f91a2118d98695fc0087dd"} [glutathione-p21795440] Deficient synthesis of glutathione underlies oxidative stress in aging and can be corrected by dietary cysteine and glycine supplementation. (2011). https://pubmed.ncbi.nlm.nih.gov/21795440/ DOI: 10.3945/ajcn.110.003483
Complete structured claim and evidence
The between-group change in urinary F2-isoprostanes was not significant (p=0.38).
Oral reduced glutathione regimen in the 2011 trial → Urinary F2-isoprostanes in the 2011 oral-GSH trial source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/21875351.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d6f87d899397204e2bfb9a70e2262ccdd14364350668fbb50906662149fc4f69", "start_char": 0, "end_char": 2042, "text_sha256": "d6f87d899397204e2bfb9a70e2262ccdd14364350668fbb50906662149fc4f69"}
experimental_model
Randomized double-blind placebo-controlled trial
exposure
GSH 500 mg twice daily for four weeks
limitations
Trial-specific null results; not proof that every dose, duration or formulation is inactive.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
The tested supplement did not improve this measured endpoint.
primary_references
[glutathione-p21875351] Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers. (2011). https://pubmed.ncbi.nlm.nih.gov/21875351/ DOI: 10.1089/acm.2010.0716
tissue_or_cell_type
40 healthy adults; 39 completed
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1152–1163
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft
### glutathione-oral-2011-isoprostane-null The between-group change in urinary F2-isoprostanes was not significant (p=0.38). Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The tested supplement did not improve this measured endpoint. organism: Human tissue_or_cell_type: 40 healthy adults; 39 completed experimental_model: Randomized double-blind placebo-controlled trial limitations: Trial-specific null results; not proof that every dose, duration or formulation is inactive. exposure: GSH 500 mg twice daily for four weeks evidence_span: {"source_cache": "artifacts/glutathione-research/21875351.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d6f87d899397204e2bfb9a70e2262ccdd14364350668fbb50906662149fc4f69", "start_char": 0, "end_char": 2042, "text_sha256": "d6f87d899397204e2bfb9a70e2262ccdd14364350668fbb50906662149fc4f69"} [glutathione-p21875351] Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers. (2011). https://pubmed.ncbi.nlm.nih.gov/21875351/ DOI: 10.1089/acm.2010.0716
Complete structured claim and evidence
The between-group change in urinary 8-OHdG was not significant (p=0.27).
Oral reduced glutathione regimen in the 2011 trial → Urinary 8-OHdG in the 2011 oral-GSH trial source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/21875351.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d6f87d899397204e2bfb9a70e2262ccdd14364350668fbb50906662149fc4f69", "start_char": 0, "end_char": 2042, "text_sha256": "d6f87d899397204e2bfb9a70e2262ccdd14364350668fbb50906662149fc4f69"}
experimental_model
Randomized double-blind placebo-controlled trial
exposure
GSH 500 mg twice daily for four weeks
limitations
Trial-specific null results; not proof that every dose, duration or formulation is inactive.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
The tested supplement did not improve this measured endpoint.
primary_references
[glutathione-p21875351] Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers. (2011). https://pubmed.ncbi.nlm.nih.gov/21875351/ DOI: 10.1089/acm.2010.0716
tissue_or_cell_type
40 healthy adults; 39 completed
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1165–1176
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft
### glutathione-oral-2011-dna-null The between-group change in urinary 8-OHdG was not significant (p=0.27). Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The tested supplement did not improve this measured endpoint. organism: Human tissue_or_cell_type: 40 healthy adults; 39 completed experimental_model: Randomized double-blind placebo-controlled trial limitations: Trial-specific null results; not proof that every dose, duration or formulation is inactive. exposure: GSH 500 mg twice daily for four weeks evidence_span: {"source_cache": "artifacts/glutathione-research/21875351.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d6f87d899397204e2bfb9a70e2262ccdd14364350668fbb50906662149fc4f69", "start_char": 0, "end_char": 2042, "text_sha256": "d6f87d899397204e2bfb9a70e2262ccdd14364350668fbb50906662149fc4f69"} [glutathione-p21875351] Effects of oral glutathione supplementation on systemic oxidative stress biomarkers in human volunteers. (2011). https://pubmed.ncbi.nlm.nih.gov/21875351/ DOI: 10.1089/acm.2010.0716
Complete structured claim and evidence
At six months, high-dose plasma GSH increased within the reported 30–35% range versus baseline.
Oral reduced glutathione regimens in the 2015 trial → Plasma glutathione concentration in the 2015 oral-GSH trial source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/24791752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388", "start_char": 0, "end_char": 1596, "text_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388"}
experimental_model
Six-month randomized double-blind placebo-controlled trial
exposure
250 or 1000 mg/day oral GSH; one-month washout
limitations
Pool increases reported relative to baseline; NK comparison was versus placebo. Biomarkers do not prove fewer illnesses or longer life.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
The measured compartment increased in the longer trial.
primary_references
[glutathione-p24791752] Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. (2015). https://pubmed.ncbi.nlm.nih.gov/24791752/ DOI: 10.1007/s00394-014-0706-z
tissue_or_cell_type
54 nonsmoking adults; immune subset
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1191–1202
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six-month randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft
### glutathione-oral-2015-plasma At six months, high-dose plasma GSH increased within the reported 30–35% range versus baseline. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The measured compartment increased in the longer trial. organism: Human tissue_or_cell_type: 54 nonsmoking adults; immune subset experimental_model: Six-month randomized double-blind placebo-controlled trial limitations: Pool increases reported relative to baseline; NK comparison was versus placebo. Biomarkers do not prove fewer illnesses or longer life. exposure: 250 or 1000 mg/day oral GSH; one-month washout evidence_span: {"source_cache": "artifacts/glutathione-research/24791752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388", "start_char": 0, "end_char": 1596, "text_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388"} [glutathione-p24791752] Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. (2015). https://pubmed.ncbi.nlm.nih.gov/24791752/ DOI: 10.1007/s00394-014-0706-z
Complete structured claim and evidence
At six months, high-dose lymphocyte GSH increased within the reported 30–35% range versus baseline.
Oral reduced glutathione regimens in the 2015 trial → Lymphocyte glutathione concentration in the 2015 oral-GSH trial source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/24791752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388", "start_char": 0, "end_char": 1596, "text_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388"}
experimental_model
Six-month randomized double-blind placebo-controlled trial
exposure
250 or 1000 mg/day oral GSH; one-month washout
limitations
Pool increases reported relative to baseline; NK comparison was versus placebo. Biomarkers do not prove fewer illnesses or longer life.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
The measured compartment increased in the longer trial.
primary_references
[glutathione-p24791752] Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. (2015). https://pubmed.ncbi.nlm.nih.gov/24791752/ DOI: 10.1007/s00394-014-0706-z
tissue_or_cell_type
54 nonsmoking adults; immune subset
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1204–1215
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six-month randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft
### glutathione-oral-2015-lymphocyte At six months, high-dose lymphocyte GSH increased within the reported 30–35% range versus baseline. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The measured compartment increased in the longer trial. organism: Human tissue_or_cell_type: 54 nonsmoking adults; immune subset experimental_model: Six-month randomized double-blind placebo-controlled trial limitations: Pool increases reported relative to baseline; NK comparison was versus placebo. Biomarkers do not prove fewer illnesses or longer life. exposure: 250 or 1000 mg/day oral GSH; one-month washout evidence_span: {"source_cache": "artifacts/glutathione-research/24791752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388", "start_char": 0, "end_char": 1596, "text_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388"} [glutathione-p24791752] Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. (2015). https://pubmed.ncbi.nlm.nih.gov/24791752/ DOI: 10.1007/s00394-014-0706-z
Complete structured claim and evidence
High-dose buccal-cell GSH increased about 260% versus baseline at six months.
Oral reduced glutathione regimens in the 2015 trial → Human exfoliated buccal-cell glutathione concentration source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/24791752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388", "start_char": 0, "end_char": 1596, "text_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388"}
experimental_model
Six-month randomized double-blind placebo-controlled trial
exposure
250 or 1000 mg/day oral GSH; one-month washout
limitations
Pool increases reported relative to baseline; NK comparison was versus placebo. Biomarkers do not prove fewer illnesses or longer life.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
The size of the change depended on the sampled compartment.
primary_references
[glutathione-p24791752] Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. (2015). https://pubmed.ncbi.nlm.nih.gov/24791752/ DOI: 10.1007/s00394-014-0706-z
tissue_or_cell_type
54 nonsmoking adults; immune subset
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1217–1228
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six-month randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft
### glutathione-oral-2015-buccal High-dose buccal-cell GSH increased about 260% versus baseline at six months. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The size of the change depended on the sampled compartment. organism: Human tissue_or_cell_type: 54 nonsmoking adults; immune subset experimental_model: Six-month randomized double-blind placebo-controlled trial limitations: Pool increases reported relative to baseline; NK comparison was versus placebo. Biomarkers do not prove fewer illnesses or longer life. exposure: 250 or 1000 mg/day oral GSH; one-month washout evidence_span: {"source_cache": "artifacts/glutathione-research/24791752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388", "start_char": 0, "end_char": 1596, "text_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388"} [glutathione-p24791752] Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. (2015). https://pubmed.ncbi.nlm.nih.gov/24791752/ DOI: 10.1007/s00394-014-0706-z
Complete structured claim and evidence
Measured GSH levels returned to baseline after the one-month washout.
Oral reduced glutathione regimens in the 2015 trial → Measured glutathione stores after washout in the 2015 trial source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/24791752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388", "start_char": 0, "end_char": 1596, "text_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388"}
experimental_model
Six-month randomized double-blind placebo-controlled trial
exposure
250 or 1000 mg/day oral GSH; one-month washout
limitations
Pool increases reported relative to baseline; NK comparison was versus placebo. Biomarkers do not prove fewer illnesses or longer life.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
The observed rise was not permanently maintained after stopping.
primary_references
[glutathione-p24791752] Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. (2015). https://pubmed.ncbi.nlm.nih.gov/24791752/ DOI: 10.1007/s00394-014-0706-z
tissue_or_cell_type
54 nonsmoking adults; immune subset
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1230–1241
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six-month randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft
### glutathione-oral-2015-washout Measured GSH levels returned to baseline after the one-month washout. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The observed rise was not permanently maintained after stopping. organism: Human tissue_or_cell_type: 54 nonsmoking adults; immune subset experimental_model: Six-month randomized double-blind placebo-controlled trial limitations: Pool increases reported relative to baseline; NK comparison was versus placebo. Biomarkers do not prove fewer illnesses or longer life. exposure: 250 or 1000 mg/day oral GSH; one-month washout evidence_span: {"source_cache": "artifacts/glutathione-research/24791752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388", "start_char": 0, "end_char": 1596, "text_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388"} [glutathione-p24791752] Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. (2015). https://pubmed.ncbi.nlm.nih.gov/24791752/ DOI: 10.1007/s00394-014-0706-z
Complete structured claim and evidence
At three months, high-dose NK cytotoxicity exceeded placebo by more than twofold in the immune subset.
Oral reduced glutathione regimens in the 2015 trial → Natural-killer-cell cytotoxicity in the 2015 GSH trial subset source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/24791752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388", "start_char": 0, "end_char": 1596, "text_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388"}
experimental_model
Six-month randomized double-blind placebo-controlled trial
exposure
250 or 1000 mg/day oral GSH; one-month washout
limitations
Pool increases reported relative to baseline; NK comparison was versus placebo. Biomarkers do not prove fewer illnesses or longer life.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
An immune assay changed; clinical infection protection was not established.
primary_references
[glutathione-p24791752] Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. (2015). https://pubmed.ncbi.nlm.nih.gov/24791752/ DOI: 10.1007/s00394-014-0706-z
tissue_or_cell_type
54 nonsmoking adults; immune subset
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1243–1254
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Six-month randomized double-blind placebo-controlled trial · source_derived_draft · unverified_draft
### glutathione-oral-2015-nk At three months, high-dose NK cytotoxicity exceeded placebo by more than twofold in the immune subset. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: An immune assay changed; clinical infection protection was not established. organism: Human tissue_or_cell_type: 54 nonsmoking adults; immune subset experimental_model: Six-month randomized double-blind placebo-controlled trial limitations: Pool increases reported relative to baseline; NK comparison was versus placebo. Biomarkers do not prove fewer illnesses or longer life. exposure: 250 or 1000 mg/day oral GSH; one-month washout evidence_span: {"source_cache": "artifacts/glutathione-research/24791752.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388", "start_char": 0, "end_char": 1596, "text_sha256": "b65406018e3d344f25ad877adb47c73cce7431e9ba5e8d280a35aae066112388"} [glutathione-p24791752] Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. (2015). https://pubmed.ncbi.nlm.nih.gov/24791752/ DOI: 10.1007/s00394-014-0706-z
Complete structured claim and evidence
GlyNAC did not significantly improve the GSH:GSSG ratio; high-dose versus placebo p=0.739.
Glycine plus N-acetylcysteine in the 114-participant two-week trial → Blood reduced-to-oxidized glutathione ratio in the 114-participant GlyNAC trial source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/35821844.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3", "start_char": 0, "end_char": 2083, "text_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3"}
experimental_model
Randomized controlled dose-ranging trial
exposure
2.4, 4.8 or 7.2 g/day GlyNAC, 1:1 ratio, for two weeks
limitations
Primary outcomes were null; the favorable low-GSH/high-MDA subgroup was post hoc and hypothesis-generating.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
Adding precursors did not reliably improve redox status in the overall trial.
primary_references
[glutathione-p35821844] A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage. (2022). https://pubmed.ncbi.nlm.nih.gov/35821844/ DOI: 10.3389/fragi.2022.852569
tissue_or_cell_type
114 healthy older volunteers; 20 young reference participants
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1256–1267
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized controlled dose-ranging trial · source_derived_draft · unverified_draft
### glutathione-glynac-large-ratio-null GlyNAC did not significantly improve the GSH:GSSG ratio; high-dose versus placebo p=0.739. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding precursors did not reliably improve redox status in the overall trial. organism: Human tissue_or_cell_type: 114 healthy older volunteers; 20 young reference participants experimental_model: Randomized controlled dose-ranging trial limitations: Primary outcomes were null; the favorable low-GSH/high-MDA subgroup was post hoc and hypothesis-generating. exposure: 2.4, 4.8 or 7.2 g/day GlyNAC, 1:1 ratio, for two weeks evidence_span: {"source_cache": "artifacts/glutathione-research/35821844.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3", "start_char": 0, "end_char": 2083, "text_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3"} [glutathione-p35821844] A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage. (2022). https://pubmed.ncbi.nlm.nih.gov/35821844/ DOI: 10.3389/fragi.2022.852569
Complete structured claim and evidence
The primary total-GSH endpoint was not significantly increased; high-dose versus placebo p=0.278.
Glycine plus N-acetylcysteine in the 114-participant two-week trial → Total blood glutathione in the 114-participant GlyNAC trial source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/35821844.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3", "start_char": 0, "end_char": 2083, "text_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3"}
experimental_model
Randomized controlled dose-ranging trial
exposure
2.4, 4.8 or 7.2 g/day GlyNAC, 1:1 ratio, for two weeks
limitations
Primary outcomes were null; the favorable low-GSH/high-MDA subgroup was post hoc and hypothesis-generating.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
The main trial result must remain visible alongside favorable subsets.
primary_references
[glutathione-p35821844] A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage. (2022). https://pubmed.ncbi.nlm.nih.gov/35821844/ DOI: 10.3389/fragi.2022.852569
tissue_or_cell_type
114 healthy older volunteers; 20 young reference participants
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1269–1280
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized controlled dose-ranging trial · source_derived_draft · unverified_draft
### glutathione-glynac-large-total-null The primary total-GSH endpoint was not significantly increased; high-dose versus placebo p=0.278. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The main trial result must remain visible alongside favorable subsets. organism: Human tissue_or_cell_type: 114 healthy older volunteers; 20 young reference participants experimental_model: Randomized controlled dose-ranging trial limitations: Primary outcomes were null; the favorable low-GSH/high-MDA subgroup was post hoc and hypothesis-generating. exposure: 2.4, 4.8 or 7.2 g/day GlyNAC, 1:1 ratio, for two weeks evidence_span: {"source_cache": "artifacts/glutathione-research/35821844.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3", "start_char": 0, "end_char": 2083, "text_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3"} [glutathione-p35821844] A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage. (2022). https://pubmed.ncbi.nlm.nih.gov/35821844/ DOI: 10.3389/fragi.2022.852569
Complete structured claim and evidence
A post-hoc high-MDA/low-baseline-GSH subgroup had higher total GSH with pooled medium/high doses (p=0.016).
Glycine plus N-acetylcysteine in the 114-participant two-week trial → Total glutathione in the high-stress/low-baseline-GSH post-hoc trial subset source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/35821844.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3", "start_char": 0, "end_char": 2083, "text_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3"}
experimental_model
Randomized controlled dose-ranging trial
exposure
2.4, 4.8 or 7.2 g/day GlyNAC, 1:1 ratio, for two weeks
limitations
Primary outcomes were null; the favorable low-GSH/high-MDA subgroup was post hoc and hypothesis-generating.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
A subgroup signal needs confirmation in a prespecified trial.
primary_references
[glutathione-p35821844] A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage. (2022). https://pubmed.ncbi.nlm.nih.gov/35821844/ DOI: 10.3389/fragi.2022.852569
tissue_or_cell_type
114 healthy older volunteers; 20 young reference participants
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1282–1293
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized controlled dose-ranging trial · source_derived_draft · unverified_draft
### glutathione-glynac-posthoc A post-hoc high-MDA/low-baseline-GSH subgroup had higher total GSH with pooled medium/high doses (p=0.016). Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: A subgroup signal needs confirmation in a prespecified trial. organism: Human tissue_or_cell_type: 114 healthy older volunteers; 20 young reference participants experimental_model: Randomized controlled dose-ranging trial limitations: Primary outcomes were null; the favorable low-GSH/high-MDA subgroup was post hoc and hypothesis-generating. exposure: 2.4, 4.8 or 7.2 g/day GlyNAC, 1:1 ratio, for two weeks evidence_span: {"source_cache": "artifacts/glutathione-research/35821844.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3", "start_char": 0, "end_char": 2083, "text_sha256": "843ee2e21e49023605a628216fb9c3c4c69ca1d8f3bb19d10da85d038d6612f3"} [glutathione-p35821844] A Randomized Controlled Clinical Trial in Healthy Older Adults to Determine Efficacy of Glycine and N-Acetylcysteine Supplementation on Glutathione Redox Status and Oxidative Damage. (2022). https://pubmed.ncbi.nlm.nih.gov/35821844/ DOI: 10.3389/fragi.2022.852569
Complete structured claim and evidence
The older GlyNAC group improved measured GSH deficiency relative to the placebo pattern.
Glycine plus N-acetylcysteine in the 24-older-adult sixteen-week trial → Measured glutathione concentrations in the 24-older-adult GlyNAC trial source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/35975308.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "13989143c2c7c77d97a84aaebdf1cb2b22fc4e44c8acb09c4f9ed3b8134b1088", "start_char": 0, "end_char": 1950, "text_sha256": "13989143c2c7c77d97a84aaebdf1cb2b22fc4e44c8acb09c4f9ed3b8134b1088"}
experimental_model
Randomized placebo-controlled trial in older adults
exposure
Sixteen-week GlyNAC versus isonitrogenous alanine placebo
limitations
Small trial, many outcomes; no demonstrated lifespan extension. Reference young group was not an additional older randomized arm.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
The small longer trial reported a biochemical benefit.
primary_references
[glutathione-p35975308] Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial. (2023). https://pubmed.ncbi.nlm.nih.gov/35975308/ DOI: 10.1093/gerona/glac135
tissue_or_cell_type
24 older adults randomized 12 per arm; 12 young reference participants
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1295–1306
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled trial in older adults · source_derived_draft · unverified_draft
### glutathione-glynac-small-gsh The older GlyNAC group improved measured GSH deficiency relative to the placebo pattern. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: The small longer trial reported a biochemical benefit. organism: Human tissue_or_cell_type: 24 older adults randomized 12 per arm; 12 young reference participants experimental_model: Randomized placebo-controlled trial in older adults limitations: Small trial, many outcomes; no demonstrated lifespan extension. Reference young group was not an additional older randomized arm. exposure: Sixteen-week GlyNAC versus isonitrogenous alanine placebo evidence_span: {"source_cache": "artifacts/glutathione-research/35975308.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "13989143c2c7c77d97a84aaebdf1cb2b22fc4e44c8acb09c4f9ed3b8134b1088", "start_char": 0, "end_char": 1950, "text_sha256": "13989143c2c7c77d97a84aaebdf1cb2b22fc4e44c8acb09c4f9ed3b8134b1088"} [glutathione-p35975308] Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial. (2023). https://pubmed.ncbi.nlm.nih.gov/35975308/ DOI: 10.1093/gerona/glac135
Complete structured claim and evidence
Investigators reported improved physical-function assessments with GlyNAC but not placebo.
Glycine plus N-acetylcysteine in the 24-older-adult sixteen-week trial → Physical-function assessments in the 24-older-adult GlyNAC trial source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/35975308.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "13989143c2c7c77d97a84aaebdf1cb2b22fc4e44c8acb09c4f9ed3b8134b1088", "start_char": 0, "end_char": 1950, "text_sha256": "13989143c2c7c77d97a84aaebdf1cb2b22fc4e44c8acb09c4f9ed3b8134b1088"}
experimental_model
Randomized placebo-controlled trial in older adults
exposure
Sixteen-week GlyNAC versus isonitrogenous alanine placebo
limitations
Small trial, many outcomes; no demonstrated lifespan extension. Reference young group was not an additional older randomized arm.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Human
plain_language
Functional signals accompany the biochemical result, with replication still needed.
primary_references
[glutathione-p35975308] Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial. (2023). https://pubmed.ncbi.nlm.nih.gov/35975308/ DOI: 10.1093/gerona/glac135
tissue_or_cell_type
24 older adults randomized 12 per arm; 12 young reference participants
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1308–1319
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Randomized placebo-controlled trial in older adults · source_derived_draft · unverified_draft
### glutathione-glynac-small-function Investigators reported improved physical-function assessments with GlyNAC but not placebo. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Functional signals accompany the biochemical result, with replication still needed. organism: Human tissue_or_cell_type: 24 older adults randomized 12 per arm; 12 young reference participants experimental_model: Randomized placebo-controlled trial in older adults limitations: Small trial, many outcomes; no demonstrated lifespan extension. Reference young group was not an additional older randomized arm. exposure: Sixteen-week GlyNAC versus isonitrogenous alanine placebo evidence_span: {"source_cache": "artifacts/glutathione-research/35975308.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "13989143c2c7c77d97a84aaebdf1cb2b22fc4e44c8acb09c4f9ed3b8134b1088", "start_char": 0, "end_char": 1950, "text_sha256": "13989143c2c7c77d97a84aaebdf1cb2b22fc4e44c8acb09c4f9ed3b8134b1088"} [glutathione-p35975308] Supplementing Glycine and N-Acetylcysteine (GlyNAC) in Older Adults Improves Glutathione Deficiency, Oxidative Stress, Mitochondrial Dysfunction, Inflammation, Physical Function, and Aging Hallmarks: A Randomized Clinical Trial. (2023). https://pubmed.ncbi.nlm.nih.gov/35975308/ DOI: 10.1093/gerona/glac135
Complete structured claim and evidence
A39 loss impaired early metastatic colonization in the tested breast-cancer models.
SLC25A39-knockout mammalian cells → Early lung colonization in SLC25A39-dependent breast-cancer models source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/40736010.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6c5baf25f027a65c991f7d45f87238cad1e474e7e910dceb32aa78a108e6d29e", "start_char": 0, "end_char": 1513, "text_sha256": "6c5baf25f027a65c991f7d45f87238cad1e474e7e910dceb32aa78a108e6d29e"}
experimental_model
Genetic screens, cancer models and patient-derived xenografts
exposure
SLC25A39 loss and ATF4 CRISPR activation
limitations
Cancer-specific mechanism; no inference that dietary or supplemental GSH causes metastasis in people.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Experimental breast-cancer cells and mouse xenografts
plain_language
Glutathione-dependent machinery can also support an unwanted cell process.
primary_references
[glutathione-p40736010] Mitochondrial Glutathione Import Enables Breast Cancer Metastasis via Integrated Stress Response Signaling. (2025). https://pubmed.ncbi.nlm.nih.gov/40736010/ DOI: 10.1158/2159-8290.cd-24-1556
tissue_or_cell_type
Early lung metastatic colonization
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1321–1332
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetic screens, cancer models and patient-derived xenografts · source_derived_draft · unverified_draft
### glutathione-metastasis-a39 A39 loss impaired early metastatic colonization in the tested breast-cancer models. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione-dependent machinery can also support an unwanted cell process. organism: Experimental breast-cancer cells and mouse xenografts tissue_or_cell_type: Early lung metastatic colonization experimental_model: Genetic screens, cancer models and patient-derived xenografts limitations: Cancer-specific mechanism; no inference that dietary or supplemental GSH causes metastasis in people. exposure: SLC25A39 loss and ATF4 CRISPR activation evidence_span: {"source_cache": "artifacts/glutathione-research/40736010.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6c5baf25f027a65c991f7d45f87238cad1e474e7e910dceb32aa78a108e6d29e", "start_char": 0, "end_char": 1513, "text_sha256": "6c5baf25f027a65c991f7d45f87238cad1e474e7e910dceb32aa78a108e6d29e"} [glutathione-p40736010] Mitochondrial Glutathione Import Enables Breast Cancer Metastasis via Integrated Stress Response Signaling. (2025). https://pubmed.ncbi.nlm.nih.gov/40736010/ DOI: 10.1158/2159-8290.cd-24-1556
Complete structured claim and evidence
Primary tumor growth was unaffected by A39 loss in the reported comparison.
SLC25A39-knockout mammalian cells → Primary tumor growth in the SLC25A39 breast-cancer study source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/40736010.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6c5baf25f027a65c991f7d45f87238cad1e474e7e910dceb32aa78a108e6d29e", "start_char": 0, "end_char": 1513, "text_sha256": "6c5baf25f027a65c991f7d45f87238cad1e474e7e910dceb32aa78a108e6d29e"}
experimental_model
Genetic screens, cancer models and patient-derived xenografts
exposure
SLC25A39 loss and ATF4 CRISPR activation
limitations
Cancer-specific mechanism; no inference that dietary or supplemental GSH causes metastasis in people.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Experimental breast-cancer cells and mouse xenografts
plain_language
Early colonization and growth of the original tumor were distinct endpoints.
primary_references
[glutathione-p40736010] Mitochondrial Glutathione Import Enables Breast Cancer Metastasis via Integrated Stress Response Signaling. (2025). https://pubmed.ncbi.nlm.nih.gov/40736010/ DOI: 10.1158/2159-8290.cd-24-1556
tissue_or_cell_type
Early lung metastatic colonization
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1334–1345
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetic screens, cancer models and patient-derived xenografts · source_derived_draft · unverified_draft
### glutathione-primary-tumor-null Primary tumor growth was unaffected by A39 loss in the reported comparison. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Early colonization and growth of the original tumor were distinct endpoints. organism: Experimental breast-cancer cells and mouse xenografts tissue_or_cell_type: Early lung metastatic colonization experimental_model: Genetic screens, cancer models and patient-derived xenografts limitations: Cancer-specific mechanism; no inference that dietary or supplemental GSH causes metastasis in people. exposure: SLC25A39 loss and ATF4 CRISPR activation evidence_span: {"source_cache": "artifacts/glutathione-research/40736010.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6c5baf25f027a65c991f7d45f87238cad1e474e7e910dceb32aa78a108e6d29e", "start_char": 0, "end_char": 1513, "text_sha256": "6c5baf25f027a65c991f7d45f87238cad1e474e7e910dceb32aa78a108e6d29e"} [glutathione-p40736010] Mitochondrial Glutathione Import Enables Breast Cancer Metastasis via Integrated Stress Response Signaling. (2025). https://pubmed.ncbi.nlm.nih.gov/40736010/ DOI: 10.1158/2159-8290.cd-24-1556
Complete structured claim and evidence
ATF4 activation restored metastatic potential in A39-deficient experimental cells.
Human activating transcription factor 4 / ATF4 → Early lung colonization in SLC25A39-dependent breast-cancer models source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/glutathione-research/40736010.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6c5baf25f027a65c991f7d45f87238cad1e474e7e910dceb32aa78a108e6d29e", "start_char": 0, "end_char": 1513, "text_sha256": "6c5baf25f027a65c991f7d45f87238cad1e474e7e910dceb32aa78a108e6d29e"}
experimental_model
Genetic screens, cancer models and patient-derived xenografts
exposure
SLC25A39 loss and ATF4 CRISPR activation
limitations
Cancer-specific mechanism; no inference that dietary or supplemental GSH causes metastasis in people.
nutrient_topic
Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
organism
Experimental breast-cancer cells and mouse xenografts
plain_language
A stress-response pathway provided a bypass in these models.
primary_references
[glutathione-p40736010] Mitochondrial Glutathione Import Enables Breast Cancer Metastasis via Integrated Stress Response Signaling. (2025). https://pubmed.ncbi.nlm.nih.gov/40736010/ DOI: 10.1158/2159-8290.cd-24-1556
tissue_or_cell_type
Early lung metastatic colonization
Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 1347–1358
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genetic screens, cancer models and patient-derived xenografts · source_derived_draft · unverified_draft
### glutathione-atf4-metastasis-rescue ATF4 activation restored metastatic potential in A39-deficient experimental cells. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: A stress-response pathway provided a bypass in these models. organism: Experimental breast-cancer cells and mouse xenografts tissue_or_cell_type: Early lung metastatic colonization experimental_model: Genetic screens, cancer models and patient-derived xenografts limitations: Cancer-specific mechanism; no inference that dietary or supplemental GSH causes metastasis in people. exposure: SLC25A39 loss and ATF4 CRISPR activation evidence_span: {"source_cache": "artifacts/glutathione-research/40736010.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6c5baf25f027a65c991f7d45f87238cad1e474e7e910dceb32aa78a108e6d29e", "start_char": 0, "end_char": 1513, "text_sha256": "6c5baf25f027a65c991f7d45f87238cad1e474e7e910dceb32aa78a108e6d29e"} [glutathione-p40736010] Mitochondrial Glutathione Import Enables Breast Cancer Metastasis via Integrated Stress Response Signaling. (2025). https://pubmed.ncbi.nlm.nih.gov/40736010/ DOI: 10.1158/2159-8290.cd-24-1556
Complete structured claim and evidence
Purified full-length human NADK catalyzed NADP+ production from NAD+ in a coupled assay supplied with 5 mM MgATP.
NADK → NADP+ source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Mg-ATP supplies the phosphate donor for generating niacin-derived NADP+. NADP+ production is distinct from its later reduction to NADPH.
evidence_span
{"source_cache": "artifacts/niacin-redox-sources/nadk-human-2025.fulltext.txt", "locator": "Results", "start_char": 53525, "end_char": 54577, "file_sha256": "72c7b9625e1bf4137d6833adac6ae49fc108f2cd75bb4945c5b04d72a0355f9b", "text_sha256": "db49fc47ad605562e1c1cf93e1b39596505906831ae509e7ec0031485f84ba4f"}
experimental_model
Full-length recombinant human NADK; G6PD-coupled assay
exposure
5 mM MgATP; 0.1–2 mM NAD+; 1 mM additional MgCl2; 30°C
limitations
Scoped experimental observation; no dietary niacin or magnesium deficiency threshold or treatment benefit was tested.
nutrient_topic
Niacin research collection; topical membership is not evidence of a direct dietary effect. · Niacin (vitamin B3)
organism
Homo sapiens
plain_language
The cytosolic kinase makes the phosphorylated cofactor using magnesium-associated ATP.
primary_references
[nadk-human-2025] Cryo-EM structure and regulation of human NAD kinase. (2025). https://pubmed.ncbi.nlm.nih.gov/39854463/ DOI: 10.1126/sciadv.ads2664
tissue_or_cell_type
Purified enzyme
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17) · lines 831–843
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Full-length recombinant human NADK; G6PD-coupled assay · source_derived_draft · unverified_draft
### b3-redox-nadk-mgatp Purified full-length human NADK catalyzed NADP+ production from NAD+ in a coupled assay supplied with 5 mM MgATP. Condition category: normal nutrient_topic: Niacin research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cytosolic kinase makes the phosphorylated cofactor using magnesium-associated ATP. organism: Homo sapiens tissue_or_cell_type: Purified enzyme experimental_model: Full-length recombinant human NADK; G6PD-coupled assay limitations: Scoped experimental observation; no dietary niacin or magnesium deficiency threshold or treatment benefit was tested. exposure: 5 mM MgATP; 0.1–2 mM NAD+; 1 mM additional MgCl2; 30°C cross_nutrient: Mg-ATP supplies the phosphate donor for generating niacin-derived NADP+. NADP+ production is distinct from its later reduction to NADPH. evidence_span: {"source_cache": "artifacts/niacin-redox-sources/nadk-human-2025.fulltext.txt", "locator": "Results", "start_char": 53525, "end_char": 54577, "file_sha256": "72c7b9625e1bf4137d6833adac6ae49fc108f2cd75bb4945c5b04d72a0355f9b", "text_sha256": "db49fc47ad605562e1c1cf93e1b39596505906831ae509e7ec0031485f84ba4f"} [nadk-human-2025] Cryo-EM structure and regulation of human NAD kinase. (2025). https://pubmed.ncbi.nlm.nih.gov/39854463/ DOI: 10.1126/sciadv.ads2664
Complete structured claim and evidence
Reconstituted human MTR transfers methylfolate-derived methyl groups through cobalamin to homocysteine, producing methionine and THF.
Cobalamin-dependent methionine synthase / MTR → L-Methionine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Folate methyl transfer requires B12.
experimental_model
Human MTR/MTRR expressed in insect cells; purified enzymes and extracts.
limitations
Chemistry, not dietary response.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Homo sapiens
plain_language
B12-dependent MTR recycles both homocysteine and folate.
primary_references
[yamada-2006] Human methionine synthase reductase is a molecular chaperone for human methionine synthase (2006). https://pubmed.ncbi.nlm.nih.gov/16769880/ DOI: 10.1073/pnas.0603694103
tissue_or_cell_type
Purified protein
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 482–492
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human MTR/MTRR expressed in insect cells; purified enzymes and extracts. · source_derived_draft · unverified_draft
### folate-methyl-mtr-methyl-transfer Reconstituted human MTR transfers methylfolate-derived methyl groups through cobalamin to homocysteine, producing methionine and THF. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: B12-dependent MTR recycles both homocysteine and folate. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Human MTR/MTRR expressed in insect cells; purified enzymes and extracts. limitations: Chemistry, not dietary response. cross_nutrient: Folate methyl transfer requires B12. [yamada-2006] Human methionine synthase reductase is a molecular chaperone for human methionine synthase (2006). https://pubmed.ncbi.nlm.nih.gov/16769880/ DOI: 10.1073/pnas.0603694103
Complete structured claim and evidence
Purified human BHMT uses betaine and homocysteine in the alternative methionine-forming reaction.
Betaine-homocysteine S-methyltransferase / BHMT → L-Methionine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Betaine/choline and folate routes meet at homocysteine.
experimental_model
Recombinant human BHMT and human liver-derived BHMT.
limitations
Does not establish complete folate substitution in vivo.
nutrient_topic
Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)
organism
Homo sapiens
plain_language
Betaine supplies another recycling route.
primary_references
[millian-1998] Human betaine-homocysteine methyltransferase is a zinc metalloenzyme (1998). https://pubmed.ncbi.nlm.nih.gov/9681996/ DOI: 10.1006/abbi.1998.0757
tissue_or_cell_type
Recombinant and liver-derived enzyme
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 610–620
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human BHMT and human liver-derived BHMT. · source_derived_draft · unverified_draft
### folate-methyl-bhmt-reaction Purified human BHMT uses betaine and homocysteine in the alternative methionine-forming reaction. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Betaine supplies another recycling route. organism: Homo sapiens tissue_or_cell_type: Recombinant and liver-derived enzyme experimental_model: Recombinant human BHMT and human liver-derived BHMT. limitations: Does not establish complete folate substitution in vivo. cross_nutrient: Betaine/choline and folate routes meet at homocysteine. [millian-1998] Human betaine-homocysteine methyltransferase is a zinc metalloenzyme (1998). https://pubmed.ncbi.nlm.nih.gov/9681996/ DOI: 10.1006/abbi.1998.0757
Complete structured claim and evidence
Glutamate-cysteine ligase joins glutamate and cysteine to form gamma-glutamylcysteine in the first glutathione-synthesis step.
Human glutamate-cysteine ligase catalytic subunit / GCLC → Gamma-glutamylcysteine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/sulforaphane-research/30581542.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77cf6674cf9b9bc140a228588a53c937966fd3a67397c1c4970221c5cc58a0b1", "start_char": 762, "end_char": 1092, "text_sha256": "927fa13b085700c20b578ecabc7c8c17a66ea4600b90809e3061d12bcaea3849"}
experimental_model
Human enzyme mutagenesis, kinetics and molecular dynamics
exposure
S-loop variants; established biosynthetic reactions described in the introduction
limitations
Reaction descriptions are background chemistry in a primary enzyme paper, not evidence that sulforaphane corrects inherited GSS deficiency.
nutrient_topic
Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study
organism
Human GSS
plain_language
The induced machinery still needs its amino-acid building blocks.
primary_references
[sulforaphane-p30581542] Genetic Mutations in the S-loop of Human Glutathione Synthetase: Links Between Substrate Binding, Active Site Structure and Allostery. (2019). https://pubmed.ncbi.nlm.nih.gov/30581542/ DOI: 10.1016/j.csbj.2018.11.008
tissue_or_cell_type
Glutathione synthesis and substrate binding
Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 840–851
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human enzyme mutagenesis, kinetics and molecular dynamics · source_derived_draft · unverified_draft
### sulforaphane-gcl-first-step Glutamate-cysteine ligase joins glutamate and cysteine to form gamma-glutamylcysteine in the first glutathione-synthesis step. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: The induced machinery still needs its amino-acid building blocks. organism: Human GSS tissue_or_cell_type: Glutathione synthesis and substrate binding experimental_model: Human enzyme mutagenesis, kinetics and molecular dynamics limitations: Reaction descriptions are background chemistry in a primary enzyme paper, not evidence that sulforaphane corrects inherited GSS deficiency. exposure: S-loop variants; established biosynthetic reactions described in the introduction evidence_span: {"source_cache": "artifacts/sulforaphane-research/30581542.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77cf6674cf9b9bc140a228588a53c937966fd3a67397c1c4970221c5cc58a0b1", "start_char": 762, "end_char": 1092, "text_sha256": "927fa13b085700c20b578ecabc7c8c17a66ea4600b90809e3061d12bcaea3849"} [sulforaphane-p30581542] Genetic Mutations in the S-loop of Human Glutathione Synthetase: Links Between Substrate Binding, Active Site Structure and Allostery. (2019). https://pubmed.ncbi.nlm.nih.gov/30581542/ DOI: 10.1016/j.csbj.2018.11.008
Complete structured claim and evidence
The human GCL holoenzyme was more active and less sensitive to glutathione inhibition than its catalytic subunit alone.
Human glutamate-cysteine ligase modifier subunit / GCLM → Human glutamate-cysteine ligase catalytic activity source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/sulforaphane-research/9637733.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4e7a66b2c4a636f70f2a5954ff304e54d4ef0f00055e53bc32ba8ceb9772fbe2", "start_char": 0, "end_char": 1258, "text_sha256": "4e7a66b2c4a636f70f2a5954ff304e54d4ef0f00055e53bc32ba8ceb9772fbe2"}
experimental_model
Purified recombinant subunit/holoenzyme kinetics
exposure
Substrate comparisons and glutathione inhibition
limitations
Baseline enzymology, not a sulforaphane or nutrient-repletion trial.
nutrient_topic
Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study
organism
Human GCLC and GCLM expressed in insect cells
plain_language
The modifier subunit changes how the glutathione-building enzyme works.
primary_references
[sulforaphane-p9637733] Expression and characterization of human glutamate-cysteine ligase. (1998). https://pubmed.ncbi.nlm.nih.gov/9637733/ DOI: 10.1006/abbi.1998.0676
tissue_or_cell_type
Glutathione synthesis first-step enzyme
Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 814–825
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant subunit/holoenzyme kinetics · source_derived_draft · unverified_draft
### sulforaphane-gclm-activity The human GCL holoenzyme was more active and less sensitive to glutathione inhibition than its catalytic subunit alone. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: The modifier subunit changes how the glutathione-building enzyme works. organism: Human GCLC and GCLM expressed in insect cells tissue_or_cell_type: Glutathione synthesis first-step enzyme experimental_model: Purified recombinant subunit/holoenzyme kinetics limitations: Baseline enzymology, not a sulforaphane or nutrient-repletion trial. exposure: Substrate comparisons and glutathione inhibition evidence_span: {"source_cache": "artifacts/sulforaphane-research/9637733.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4e7a66b2c4a636f70f2a5954ff304e54d4ef0f00055e53bc32ba8ceb9772fbe2", "start_char": 0, "end_char": 1258, "text_sha256": "4e7a66b2c4a636f70f2a5954ff304e54d4ef0f00055e53bc32ba8ceb9772fbe2"} [sulforaphane-p9637733] Expression and characterization of human glutamate-cysteine ligase. (1998). https://pubmed.ncbi.nlm.nih.gov/9637733/ DOI: 10.1006/abbi.1998.0676
Complete structured claim and evidence
Glutathione inhibited both human GCLC and GCL holoenzyme, with greater sensitivity of GCLC alone.
GSH → Human glutamate-cysteine ligase catalytic activity source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/sulforaphane-research/9637733.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4e7a66b2c4a636f70f2a5954ff304e54d4ef0f00055e53bc32ba8ceb9772fbe2", "start_char": 0, "end_char": 1258, "text_sha256": "4e7a66b2c4a636f70f2a5954ff304e54d4ef0f00055e53bc32ba8ceb9772fbe2"}
experimental_model
Purified recombinant subunit/holoenzyme kinetics
exposure
Substrate comparisons and glutathione inhibition
limitations
Baseline enzymology, not a sulforaphane or nutrient-repletion trial.
nutrient_topic
Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study
organism
Human GCLC and GCLM expressed in insect cells
plain_language
The product feeds back on the machinery that makes more of it.
primary_references
[sulforaphane-p9637733] Expression and characterization of human glutamate-cysteine ligase. (1998). https://pubmed.ncbi.nlm.nih.gov/9637733/ DOI: 10.1006/abbi.1998.0676
tissue_or_cell_type
Glutathione synthesis first-step enzyme
Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 827–838
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant subunit/holoenzyme kinetics · source_derived_draft · unverified_draft
### sulforaphane-gsh-feedback Glutathione inhibited both human GCLC and GCL holoenzyme, with greater sensitivity of GCLC alone. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: The product feeds back on the machinery that makes more of it. organism: Human GCLC and GCLM expressed in insect cells tissue_or_cell_type: Glutathione synthesis first-step enzyme experimental_model: Purified recombinant subunit/holoenzyme kinetics limitations: Baseline enzymology, not a sulforaphane or nutrient-repletion trial. exposure: Substrate comparisons and glutathione inhibition evidence_span: {"source_cache": "artifacts/sulforaphane-research/9637733.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "4e7a66b2c4a636f70f2a5954ff304e54d4ef0f00055e53bc32ba8ceb9772fbe2", "start_char": 0, "end_char": 1258, "text_sha256": "4e7a66b2c4a636f70f2a5954ff304e54d4ef0f00055e53bc32ba8ceb9772fbe2"} [sulforaphane-p9637733] Expression and characterization of human glutamate-cysteine ligase. (1998). https://pubmed.ncbi.nlm.nih.gov/9637733/ DOI: 10.1006/abbi.1998.0676
Complete structured claim and evidence
Human GSS joins gamma-glutamylcysteine and glycine in an ATP-dependent reaction to form glutathione.
Human glutathione synthetase / GSS → GSH source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/sulforaphane-research/30581542.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77cf6674cf9b9bc140a228588a53c937966fd3a67397c1c4970221c5cc58a0b1", "start_char": 923, "end_char": 1092, "text_sha256": "bed9ef1323b513b1e31b65277f28b935ddf0c9b0c83cbe9ee9f827f97806846c"}
experimental_model
Human enzyme mutagenesis, kinetics and molecular dynamics
exposure
S-loop variants; established biosynthetic reactions described in the introduction
limitations
Reaction descriptions are background chemistry in a primary enzyme paper, not evidence that sulforaphane corrects inherited GSS deficiency.
nutrient_topic
Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study
organism
Human GSS
plain_language
A second enzyme, glycine and energy complete the molecule.
primary_references
[sulforaphane-p30581542] Genetic Mutations in the S-loop of Human Glutathione Synthetase: Links Between Substrate Binding, Active Site Structure and Allostery. (2019). https://pubmed.ncbi.nlm.nih.gov/30581542/ DOI: 10.1016/j.csbj.2018.11.008
tissue_or_cell_type
Glutathione synthesis and substrate binding
Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 853–864
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human enzyme mutagenesis, kinetics and molecular dynamics · source_derived_draft · unverified_draft
### sulforaphane-gss-second-step Human GSS joins gamma-glutamylcysteine and glycine in an ATP-dependent reaction to form glutathione. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second enzyme, glycine and energy complete the molecule. organism: Human GSS tissue_or_cell_type: Glutathione synthesis and substrate binding experimental_model: Human enzyme mutagenesis, kinetics and molecular dynamics limitations: Reaction descriptions are background chemistry in a primary enzyme paper, not evidence that sulforaphane corrects inherited GSS deficiency. exposure: S-loop variants; established biosynthetic reactions described in the introduction evidence_span: {"source_cache": "artifacts/sulforaphane-research/30581542.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "77cf6674cf9b9bc140a228588a53c937966fd3a67397c1c4970221c5cc58a0b1", "start_char": 923, "end_char": 1092, "text_sha256": "bed9ef1323b513b1e31b65277f28b935ddf0c9b0c83cbe9ee9f827f97806846c"} [sulforaphane-p30581542] Genetic Mutations in the S-loop of Human Glutathione Synthetase: Links Between Substrate Binding, Active Site Structure and Allostery. (2019). https://pubmed.ncbi.nlm.nih.gov/30581542/ DOI: 10.1016/j.csbj.2018.11.008
Complete structured claim and evidence
GSR reduces one glutathione-disulfide molecule to two reduced glutathione molecules using the NADPH/FAD catalytic relay.
Glutathione reductase / GSR → GSSG source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B2-FAD supports GSH recycling; selenium-dependent GPX use of GSH is a separate reaction.
evidence_location
Results: NADPH binding; Fig 1 consensus cycle; GSH/GSSG complexes
experimental_model
Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls.
exposure
Purified-enzyme assay
limitations
GSR is not glutathione peroxidase; this record does not show that B2 improves selenium repletion.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
This enzyme recycles glutathione after oxidation.
primary_references
[berkholz2008] Catalytic cycle of human glutathione reductase near 1 A resolution. (2008). https://pubmed.ncbi.nlm.nih.gov/18638483/ DOI: 10.1016/j.jmb.2008.06.083
tissue_or_cell_type
Purified human GSR
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1332–1344
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls. · source_derived_draft · unverified_draft
### b2-gsr-gssg-to-gsh GSR reduces one glutathione-disulfide molecule to two reduced glutathione molecules using the NADPH/FAD catalytic relay. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: This enzyme recycles glutathione after oxidation. organism: Homo sapiens tissue_or_cell_type: Purified human GSR experimental_model: Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls. limitations: GSR is not glutathione peroxidase; this record does not show that B2 improves selenium repletion. exposure: Purified-enzyme assay cross_nutrient: B2-FAD supports GSH recycling; selenium-dependent GPX use of GSH is a separate reaction. evidence_location: Results: NADPH binding; Fig 1 consensus cycle; GSH/GSSG complexes [berkholz2008] Catalytic cycle of human glutathione reductase near 1 A resolution. (2008). https://pubmed.ncbi.nlm.nih.gov/18638483/ DOI: 10.1016/j.jmb.2008.06.083
Complete structured claim and evidence
The GSR catalytic cycle transfers reducing equivalents from flavin to the Cys58-Cys63 active-site disulfide before glutathione-disulfide reduction.
FAD → Glutathione reductase / GSR source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B2-derived cofactor bridges NADPH and the glutathione system.
evidence_location
Results: NADPH binding; Fig 1 consensus cycle; GSH/GSSG complexes
experimental_model
Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls.
exposure
Purified-enzyme assay
limitations
Mechanism integrates natural-substrate structures with prior kinetic work; transient intermediates were not all directly trapped here.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
FAD relays electrons through enzyme cysteines.
primary_references
[berkholz2008] Catalytic cycle of human glutathione reductase near 1 A resolution. (2008). https://pubmed.ncbi.nlm.nih.gov/18638483/ DOI: 10.1016/j.jmb.2008.06.083
tissue_or_cell_type
Purified human GSR
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1318–1330
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls. · source_derived_draft · unverified_draft
### b2-gsr-flavin-disulfide-relay The GSR catalytic cycle transfers reducing equivalents from flavin to the Cys58-Cys63 active-site disulfide before glutathione-disulfide reduction. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: FAD relays electrons through enzyme cysteines. organism: Homo sapiens tissue_or_cell_type: Purified human GSR experimental_model: Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls. limitations: Mechanism integrates natural-substrate structures with prior kinetic work; transient intermediates were not all directly trapped here. exposure: Purified-enzyme assay cross_nutrient: B2-derived cofactor bridges NADPH and the glutathione system. evidence_location: Results: NADPH binding; Fig 1 consensus cycle; GSH/GSSG complexes [berkholz2008] Catalytic cycle of human glutathione reductase near 1 A resolution. (2008). https://pubmed.ncbi.nlm.nih.gov/18638483/ DOI: 10.1016/j.jmb.2008.06.083
Complete structured claim and evidence
Human GSR substrate structures place NADPH for hydride transfer to bound FAD, the first redox step in glutathione recycling.
NADPH → FAD source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Nicotinamide-containing NADPH and B2-derived FAD perform distinct functions.
evidence_location
Results: NADPH binding; Fig 1 consensus cycle; GSH/GSSG complexes
experimental_model
Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls.
exposure
Purified-enzyme assay
limitations
Structural support for the established catalytic cycle; radiation reduction must be distinguished from natural catalysis.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
NADPH supplies electrons to the B2-derived cofactor.
primary_references
[berkholz2008] Catalytic cycle of human glutathione reductase near 1 A resolution. (2008). https://pubmed.ncbi.nlm.nih.gov/18638483/ DOI: 10.1016/j.jmb.2008.06.083
tissue_or_cell_type
Purified human erythrocyte-type GSR crystals
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1304–1316
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls. · source_derived_draft · unverified_draft
### b2-gsr-nadph-to-fad Human GSR substrate structures place NADPH for hydride transfer to bound FAD, the first redox step in glutathione recycling. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: NADPH supplies electrons to the B2-derived cofactor. organism: Homo sapiens tissue_or_cell_type: Purified human erythrocyte-type GSR crystals experimental_model: Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls. limitations: Structural support for the established catalytic cycle; radiation reduction must be distinguished from natural catalysis. exposure: Purified-enzyme assay cross_nutrient: Nicotinamide-containing NADPH and B2-derived FAD perform distinct functions. evidence_location: Results: NADPH binding; Fig 1 consensus cycle; GSH/GSSG complexes [berkholz2008] Catalytic cycle of human glutathione reductase near 1 A resolution. (2008). https://pubmed.ncbi.nlm.nih.gov/18638483/ DOI: 10.1016/j.jmb.2008.06.083
Complete structured claim and evidence
Human RFK phosphorylates riboflavin to FMN using ATP, yielding ADP; this precedes FLAD1-mediated FAD synthesis.
Riboflavin kinase / RFK → Riboflavin (vitamin B2) source_derived_draftungraded
Experimental context and source evidence
evidence_location
Abstract and product-bound structure
experimental_model
Human RFK structural and catalytic mechanism study
exposure
Purified RFK with flavin and adenine nucleotide ligands.
limitations
Reaction chemistry does not imply RFK controls every tissue flavin pool to the same extent.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
RFK performs the first activation step from riboflavin to FMN.
primary_references
[transport-rfk-2003] Ligand binding-induced conformational changes in riboflavin kinase: structural basis for the ordered mechanism. (2003). https://pubmed.ncbi.nlm.nih.gov/14580199/ DOI: 10.1021/bi035450t
tissue_or_cell_type
Purified protein
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 293–304
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human RFK structural and catalytic mechanism study · source_derived_draft · unverified_draft
### transport-rfk-phosphorylation Human RFK phosphorylates riboflavin to FMN using ATP, yielding ADP; this precedes FLAD1-mediated FAD synthesis. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: RFK performs the first activation step from riboflavin to FMN. organism: Homo sapiens tissue_or_cell_type: Purified protein experimental_model: Human RFK structural and catalytic mechanism study limitations: Reaction chemistry does not imply RFK controls every tissue flavin pool to the same extent. exposure: Purified RFK with flavin and adenine nucleotide ligands. evidence_location: Abstract and product-bound structure [transport-rfk-2003] Ligand binding-induced conformational changes in riboflavin kinase: structural basis for the ordered mechanism. (2003). https://pubmed.ncbi.nlm.nih.gov/14580199/ DOI: 10.1021/bi035450t
Complete structured claim and evidence
Marginally B2-deficient subjects had lower erythrocyte glutathione reductase activity than controls across the study comparison.
Riboflavin (vitamin B2) → Erythrocyte glutathione reductase activity source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
B2 supports a component of glutathione recycling; this is not proof of universal glutathione exhaustion.
experimental_model
Erythrocytes from marginally riboflavin-deficient people and controls separated into nine density fractions.
exposure
Red-cell age-fraction enzyme/cofactor assays, glutathione, hemoglobin species and peroxide susceptibility; observational comparison.
limitations
Observational age-fraction study; reduced glutathione itself was not among the significant between-group differences.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
A B2-dependent recycling enzyme was less active in red cells from the deficient group.
primary_references
[b2-powers1981] Riboflavin deficiency in man: effects on haemoglobin and reduced glutathione in erythrocytes of different ages (1981). https://pubmed.ncbi.nlm.nih.gov/7284295/ DOI: 10.1079/bjn19810031
tissue_or_cell_type
Human clinical setting
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1692–1703
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Erythrocytes from marginally riboflavin-deficient people and controls separated into nine density fractions. · source_derived_draft · unverified_draft
### b2-deficiency-redcell-gsr Marginally B2-deficient subjects had lower erythrocyte glutathione reductase activity than controls across the study comparison. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A B2-dependent recycling enzyme was less active in red cells from the deficient group. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Erythrocytes from marginally riboflavin-deficient people and controls separated into nine density fractions. limitations: Observational age-fraction study; reduced glutathione itself was not among the significant between-group differences. exposure: Red-cell age-fraction enzyme/cofactor assays, glutathione, hemoglobin species and peroxide susceptibility; observational comparison. cross_nutrient: B2 supports a component of glutathione recycling; this is not proof of universal glutathione exhaustion. [b2-powers1981] Riboflavin deficiency in man: effects on haemoglobin and reduced glutathione in erythrocytes of different ages (1981). https://pubmed.ncbi.nlm.nih.gov/7284295/ DOI: 10.1079/bjn19810031
Complete structured claim and evidence
In G6PD-deficient erythrocytes, glutathione reductase was usually already FAD-saturated despite evidence of low FMN-dependent oxidase activity.
Glucose-6-phosphate dehydrogenase / G6PD → Erythrocyte glutathione reductase activation coefficient / EGRAC source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
cross_nutrient
G6PD genotype and distinct flavin pools alter interpretation of B2/B6-linked assays.
experimental_model
Human erythrocytes from G6PD deficiency, heterozygous beta-thalassemia and controls.
exposure
In-vitro FAD stimulation of glutathione reductase and PNP oxidase activity, with oral-riboflavin response observations.
limitations
Human red-cell observation; the proposed faster FMN-to-FAD flux was an interpretation, not a directly measured universal mechanism.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Homo sapiens
plain_language
A red-cell FAD saturation test can look adequate while another B2-dependent enzyme system is poorly supplied.
primary_references
[b2-anderson1987] Glutathione reductase activity and its relationship to pyridoxine phosphate activity in G6PD deficiency (1987). https://pubmed.ncbi.nlm.nih.gov/3582603/ DOI: 10.1111/j.1600-0609.1987.tb01417.x
tissue_or_cell_type
Human clinical setting
trigger_kind
biomarker_context Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1666–1677
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human erythrocytes from G6PD deficiency, heterozygous beta-thalassemia and controls. · source_derived_draft · unverified_draft
### b2-g6pd-fad-assay-limit In G6PD-deficient erythrocytes, glutathione reductase was usually already FAD-saturated despite evidence of low FMN-dependent oxidase activity. Condition category: biomarker_context nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A red-cell FAD saturation test can look adequate while another B2-dependent enzyme system is poorly supplied. organism: Homo sapiens tissue_or_cell_type: Human clinical setting experimental_model: Human erythrocytes from G6PD deficiency, heterozygous beta-thalassemia and controls. limitations: Human red-cell observation; the proposed faster FMN-to-FAD flux was an interpretation, not a directly measured universal mechanism. exposure: In-vitro FAD stimulation of glutathione reductase and PNP oxidase activity, with oral-riboflavin response observations. cross_nutrient: G6PD genotype and distinct flavin pools alter interpretation of B2/B6-linked assays. [b2-anderson1987] Glutathione reductase activity and its relationship to pyridoxine phosphate activity in G6PD deficiency (1987). https://pubmed.ncbi.nlm.nih.gov/3582603/ DOI: 10.1111/j.1600-0609.1987.tb01417.x
Complete structured claim and evidence
PLP-dependent human CBS condenses serine with homocysteine to produce cystathionine.
Human cystathionine beta-synthase / CBS → Cystathionine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Methionine-derived sulfur enters cysteine synthesis.
experimental_model
Recombinant truncated human CBS crystallography
limitations
Enzyme chemistry alone does not predict whole-body homocysteine during mild deficiency.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
This B6-dependent step channels homocysteine into transsulfuration.
primary_references
[b6-cbs-2001] Structure of human cystathionine beta-synthase: a unique pyridoxal 5'-phosphate-dependent heme protein. (2001). https://pmc.ncbi.nlm.nih.gov/articles/PMC149156/ DOI: 10.1093/emboj/20.15.3910
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 517–527
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant truncated human CBS crystallography · source_derived_draft · unverified_draft
### b6-met-cbs-condensation PLP-dependent human CBS condenses serine with homocysteine to produce cystathionine. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This B6-dependent step channels homocysteine into transsulfuration. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant truncated human CBS crystallography limitations: Enzyme chemistry alone does not predict whole-body homocysteine during mild deficiency. cross_nutrient: Methionine-derived sulfur enters cysteine synthesis. [b6-cbs-2001] Structure of human cystathionine beta-synthase: a unique pyridoxal 5'-phosphate-dependent heme protein. (2001). https://pmc.ncbi.nlm.nih.gov/articles/PMC149156/ DOI: 10.1093/emboj/20.15.3910
Complete structured claim and evidence
Human CTH cleaves cystathionine to cysteine, 2-oxobutanoate and ammonia in a PLP-dependent reaction.
Human cystathionine gamma-lyase / CTH → Cystathionine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B6-dependent sulfur transfer supplies cysteine; glutathione synthesis requires additional enzymes.
experimental_model
Purified human CTH apo/holo crystal structures and assays
limitations
Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
This step releases cysteine for downstream metabolism.
primary_references
[b6-cth-structure-2009] Structural Basis for the Inhibition Mechanism of Human Cystathionine gamma-Lyase, an Enzyme Responsible for the Production of H2S (2009). https://doi.org/10.1074/jbc.M805459200 DOI: 10.1074/jbc.M805459200
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 554–564
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human CTH apo/holo crystal structures and assays · source_derived_draft · unverified_draft
### b6-met-cth-cleavage Human CTH cleaves cystathionine to cysteine, 2-oxobutanoate and ammonia in a PLP-dependent reaction. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This step releases cysteine for downstream metabolism. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human CTH apo/holo crystal structures and assays limitations: Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds. cross_nutrient: B6-dependent sulfur transfer supplies cysteine; glutathione synthesis requires additional enzymes. [b6-cth-structure-2009] Structural Basis for the Inhibition Mechanism of Human Cystathionine gamma-Lyase, an Enzyme Responsible for the Production of H2S (2009). https://doi.org/10.1074/jbc.M805459200 DOI: 10.1074/jbc.M805459200
Complete structured claim and evidence
Human SHMT1 uses PLP to couple serine-to-glycine conversion with transfer of a one-carbon unit to tetrahydrofolate.
SHMT1 → 5,10-Methylenetetrahydrofolate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
PLP (B6) and THF (folate) cooperate in one reaction.
experimental_model
Purified human SHMT1 and SHMT2; structures and solution oligomerization
limitations
Reaction is reversible; assembly assays do not establish flux in every cell.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The enzyme connects B6-dependent amino-acid chemistry to folate chemistry.
primary_references
[b6-shmt-2015] How pyridoxal 5'-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state (2015). https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.13211 DOI: 10.1111/febs.13211
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 602–612
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human SHMT1 and SHMT2; structures and solution oligomerization · source_derived_draft · unverified_draft
### b6-met-shmt1-onecarbon Human SHMT1 uses PLP to couple serine-to-glycine conversion with transfer of a one-carbon unit to tetrahydrofolate. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme connects B6-dependent amino-acid chemistry to folate chemistry. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human SHMT1 and SHMT2; structures and solution oligomerization limitations: Reaction is reversible; assembly assays do not establish flux in every cell. cross_nutrient: PLP (B6) and THF (folate) cooperate in one reaction. [b6-shmt-2015] How pyridoxal 5'-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state (2015). https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.13211 DOI: 10.1111/febs.13211
Complete structured claim and evidence
Human SHMT2 uses PLP to couple serine-to-glycine conversion with transfer of a one-carbon unit to tetrahydrofolate.
SHMT2 → 5,10-Methylenetetrahydrofolate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
PLP (B6) and THF (folate) cooperate in one reaction.
experimental_model
Purified human SHMT1 and SHMT2; structures and solution oligomerization
limitations
Reaction is reversible; assembly assays do not establish flux in every cell.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The enzyme connects B6-dependent amino-acid chemistry to folate chemistry.
primary_references
[b6-shmt-2015] How pyridoxal 5'-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state (2015). https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.13211 DOI: 10.1111/febs.13211
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 614–624
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human SHMT1 and SHMT2; structures and solution oligomerization · source_derived_draft · unverified_draft
### b6-met-shmt2-onecarbon Human SHMT2 uses PLP to couple serine-to-glycine conversion with transfer of a one-carbon unit to tetrahydrofolate. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme connects B6-dependent amino-acid chemistry to folate chemistry. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Purified human SHMT1 and SHMT2; structures and solution oligomerization limitations: Reaction is reversible; assembly assays do not establish flux in every cell. cross_nutrient: PLP (B6) and THF (folate) cooperate in one reaction. [b6-shmt-2015] How pyridoxal 5'-phosphate differentially regulates human cytosolic and mitochondrial serine hydroxymethyltransferase oligomeric state (2015). https://febs.onlinelibrary.wiley.com/doi/10.1111/febs.13211 DOI: 10.1111/febs.13211
Complete structured claim and evidence
Tracing in a cultured human hepatoma cell line estimated that transsulfuration supplied homocysteine-derived sulfur to approximately half of the intracellular glutathione pool.
Homocysteine → GSH source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
B6-dependent transsulfuration connects methionine/homocysteine to the cysteine supply for glutathione.
experimental_model
Cultured human hepatoma cell line; metabolic sulfur tracing
limitations
Fraction is culture-specific and traces sulfur, not all glutathione atoms; this experiment did not measure dietary B6 depletion.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
In this cell system, sulfur routed through B6-dependent enzymes helped supply glutathione.
primary_references
[b6-glutathione-2000] The quantitatively important relationship between homocysteine metabolism and glutathione synthesis by the transsulfuration pathway and its regulation by redox changes (2000). https://pubmed.ncbi.nlm.nih.gov/11041866/ DOI: 10.1021/bi001088w
tissue_or_cell_type
Cultured human hepatoma cell line
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 590–600
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cultured human hepatoma cell line; metabolic sulfur tracing · source_derived_draft · unverified_draft
### b6-met-transsulfuration-glutathione Tracing in a cultured human hepatoma cell line estimated that transsulfuration supplied homocysteine-derived sulfur to approximately half of the intracellular glutathione pool. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: In this cell system, sulfur routed through B6-dependent enzymes helped supply glutathione. organism: Homo sapiens tissue_or_cell_type: Cultured human hepatoma cell line experimental_model: Cultured human hepatoma cell line; metabolic sulfur tracing limitations: Fraction is culture-specific and traces sulfur, not all glutathione atoms; this experiment did not measure dietary B6 depletion. cross_nutrient: B6-dependent transsulfuration connects methionine/homocysteine to the cysteine supply for glutathione. [b6-glutathione-2000] The quantitatively important relationship between homocysteine metabolism and glutathione synthesis by the transsulfuration pathway and its regulation by redox changes (2000). https://pubmed.ncbi.nlm.nih.gov/11041866/ DOI: 10.1021/bi001088w
Complete structured claim and evidence
Dietary B6 restriction increased plasma cystathionine by 124% while plasma PLP fell from 55.1 to 22.6 nmol/L.
Vitamin B6 → Cystathionine source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
experimental_model
Nine healthy adults (five women, four men; ages 20–30), controlled restriction with fasting stable-isotope measurements.
exposure
Four weeks below 0.5 mg/day dietary B6; overnight-fasted tracer protocol.
limitations
Pool size alone cannot identify the limiting enzyme or quantify pathway flux.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
A pathway intermediate accumulated even though the whole pathway did not simply stop.
primary_references
[b6-davis2006] Plasma glutathione and cystathionine concentrations are elevated but cysteine flux is unchanged by dietary vitamin B-6 restriction in young men and women (2006). https://pubmed.ncbi.nlm.nih.gov/16424114/ DOI: 10.1093/jn/136.2.373
tissue_or_cell_type
Human blood and whole-body measurements
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1309–1319
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nine healthy adults (five women, four men; ages 20–30), controlled restriction with fasting stable-isotope measurements. · source_derived_draft · unverified_draft
### b6-fasting-cystathionine-pool Dietary B6 restriction increased plasma cystathionine by 124% while plasma PLP fell from 55.1 to 22.6 nmol/L. Condition category: nutrient_deficiency nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A pathway intermediate accumulated even though the whole pathway did not simply stop. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Nine healthy adults (five women, four men; ages 20–30), controlled restriction with fasting stable-isotope measurements. limitations: Pool size alone cannot identify the limiting enzyme or quantify pathway flux. exposure: Four weeks below 0.5 mg/day dietary B6; overnight-fasted tracer protocol. [b6-davis2006] Plasma glutathione and cystathionine concentrations are elevated but cysteine flux is unchanged by dietary vitamin B-6 restriction in young men and women (2006). https://pubmed.ncbi.nlm.nih.gov/16424114/ DOI: 10.1093/jn/136.2.373
Complete structured claim and evidence
Plasma total glutathione rose 38% during restriction; plasma cysteine, homocysteine and CRP did not significantly change.
Vitamin B6 → Plasma total glutathione concentration source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
B6-dependent sulfur metabolism connects to glutathione, with blood and cellular pools distinguished.
experimental_model
Nine healthy adults (five women, four men; ages 20–30), controlled restriction with fasting stable-isotope measurements.
exposure
Four weeks below 0.5 mg/day dietary B6; overnight-fasted tracer protocol.
limitations
Plasma total glutathione is not intracellular reduced GSH, tissue antioxidant capacity or synthesis rate.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
This experiment did not find a universal glutathione collapse.
primary_references
[b6-davis2006] Plasma glutathione and cystathionine concentrations are elevated but cysteine flux is unchanged by dietary vitamin B-6 restriction in young men and women (2006). https://pubmed.ncbi.nlm.nih.gov/16424114/ DOI: 10.1093/jn/136.2.373
tissue_or_cell_type
Human blood and whole-body measurements
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1321–1332
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nine healthy adults (five women, four men; ages 20–30), controlled restriction with fasting stable-isotope measurements. · source_derived_draft · unverified_draft
### b6-fasting-total-glutathione Plasma total glutathione rose 38% during restriction; plasma cysteine, homocysteine and CRP did not significantly change. Condition category: nutrient_deficiency nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: This experiment did not find a universal glutathione collapse. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Nine healthy adults (five women, four men; ages 20–30), controlled restriction with fasting stable-isotope measurements. limitations: Plasma total glutathione is not intracellular reduced GSH, tissue antioxidant capacity or synthesis rate. exposure: Four weeks below 0.5 mg/day dietary B6; overnight-fasted tracer protocol. cross_nutrient: B6-dependent sulfur metabolism connects to glutathione, with blood and cellular pools distinguished. [b6-davis2006] Plasma glutathione and cystathionine concentrations are elevated but cysteine flux is unchanged by dietary vitamin B-6 restriction in young men and women (2006). https://pubmed.ncbi.nlm.nih.gov/16424114/ DOI: 10.1093/jn/136.2.373
Complete structured claim and evidence
Whole-body cysteine flux and fractional cystathionine synthesis were unchanged; transsulfuration-derived cysteine synthesis was below detection in this fasting protocol.
Vitamin B6 → Whole-body cysteine flux source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
experimental_model
Nine healthy adults (five women, four men; ages 20–30), controlled restriction with fasting stable-isotope measurements.
exposure
Four weeks below 0.5 mg/day dietary B6; overnight-fasted tracer protocol.
limitations
Below detection is not zero flux, nor proof that transsulfuration was unchanged.
nutrient_topic
Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
organism
Homo sapiens
plain_language
The investigators could measure cysteine turnover but could not reliably quantify one specific input route.
primary_references
[b6-davis2006] Plasma glutathione and cystathionine concentrations are elevated but cysteine flux is unchanged by dietary vitamin B-6 restriction in young men and women (2006). https://pubmed.ncbi.nlm.nih.gov/16424114/ DOI: 10.1093/jn/136.2.373
tissue_or_cell_type
Human blood and whole-body measurements
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1334–1344
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Nine healthy adults (five women, four men; ages 20–30), controlled restriction with fasting stable-isotope measurements. · source_derived_draft · unverified_draft
### b6-fasting-cysteine-flux Whole-body cysteine flux and fractional cystathionine synthesis were unchanged; transsulfuration-derived cysteine synthesis was below detection in this fasting protocol. Condition category: nutrient_deficiency nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The investigators could measure cysteine turnover but could not reliably quantify one specific input route. organism: Homo sapiens tissue_or_cell_type: Human blood and whole-body measurements experimental_model: Nine healthy adults (five women, four men; ages 20–30), controlled restriction with fasting stable-isotope measurements. limitations: Below detection is not zero flux, nor proof that transsulfuration was unchanged. exposure: Four weeks below 0.5 mg/day dietary B6; overnight-fasted tracer protocol. [b6-davis2006] Plasma glutathione and cystathionine concentrations are elevated but cysteine flux is unchanged by dietary vitamin B-6 restriction in young men and women (2006). https://pubmed.ncbi.nlm.nih.gov/16424114/ DOI: 10.1093/jn/136.2.373
Complete structured claim and evidence
Human MMACHC transfers the 5′-deoxyadenosyl group from adenosylcobalamin to glutathione, yielding cob(I)alamin and the corresponding glutathione thioether; reported turnover was 0.174 +/- 0.006 per hour at 20 C.
Human MMACHC / cobalamin-processing protein CblC → 5'-Deoxyadenosylcobalamin source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary abstract; indexed article Introduction/Figure 1
experimental_model
Purified human MMACHC substrate chemistry
exposure
Specified alkylcobalamin plus GSH; kinetic temperature 20 C
limitations
Reconstituted biochemical system; establishes reaction capability rather than the quantitatively dominant pathway in living humans.
nutrient_topic
Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
organism
Homo sapiens
plain_language
Glutathione receives the side group removed from this B12 form.
primary_references
[kim-2009-gsh-dealkylation] A human vitamin B12 trafficking protein uses glutathione transferase activity for processing alkylcobalamins (2009). https://pubmed.ncbi.nlm.nih.gov/19801555/ DOI: 10.1074/jbc.M109.057877
tissue_or_cell_type
Cell-free assay
Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 725–737
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human MMACHC substrate chemistry · source_derived_draft · unverified_draft
### b12-mmachc-adenosyl-dealkylation Human MMACHC transfers the 5′-deoxyadenosyl group from adenosylcobalamin to glutathione, yielding cob(I)alamin and the corresponding glutathione thioether; reported turnover was 0.174 +/- 0.006 per hour at 20 C. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione receives the side group removed from this B12 form. organism: Homo sapiens tissue_or_cell_type: Cell-free assay experimental_model: Purified human MMACHC substrate chemistry limitations: Reconstituted biochemical system; establishes reaction capability rather than the quantitatively dominant pathway in living humans. exposure: Specified alkylcobalamin plus GSH; kinetic temperature 20 C cross_nutrient: true evidence_location: Primary abstract; indexed article Introduction/Figure 1 [kim-2009-gsh-dealkylation] A human vitamin B12 trafficking protein uses glutathione transferase activity for processing alkylcobalamins (2009). https://pubmed.ncbi.nlm.nih.gov/19801555/ DOI: 10.1074/jbc.M109.057877
Complete structured claim and evidence
Human MMACHC transfers the methyl group from methylcobalamin to glutathione, yielding cob(I)alamin and the corresponding glutathione thioether; reported turnover was 11.7 +/- 0.2 per hour at 20 C.
Human MMACHC / cobalamin-processing protein CblC → Methylcobalamin source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary abstract; indexed article Introduction/Figure 1
experimental_model
Purified human MMACHC substrate chemistry
exposure
Specified alkylcobalamin plus GSH; kinetic temperature 20 C
limitations
Reconstituted biochemical system; establishes reaction capability rather than the quantitatively dominant pathway in living humans.
nutrient_topic
Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
organism
Homo sapiens
plain_language
Glutathione receives the side group removed from this B12 form.
primary_references
[kim-2009-gsh-dealkylation] A human vitamin B12 trafficking protein uses glutathione transferase activity for processing alkylcobalamins (2009). https://pubmed.ncbi.nlm.nih.gov/19801555/ DOI: 10.1074/jbc.M109.057877
tissue_or_cell_type
Cell-free assay
Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 711–723
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human MMACHC substrate chemistry · source_derived_draft · unverified_draft
### b12-mmachc-methyl-dealkylation Human MMACHC transfers the methyl group from methylcobalamin to glutathione, yielding cob(I)alamin and the corresponding glutathione thioether; reported turnover was 11.7 +/- 0.2 per hour at 20 C. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione receives the side group removed from this B12 form. organism: Homo sapiens tissue_or_cell_type: Cell-free assay experimental_model: Purified human MMACHC substrate chemistry limitations: Reconstituted biochemical system; establishes reaction capability rather than the quantitatively dominant pathway in living humans. exposure: Specified alkylcobalamin plus GSH; kinetic temperature 20 C cross_nutrient: true evidence_location: Primary abstract; indexed article Introduction/Figure 1 [kim-2009-gsh-dealkylation] A human vitamin B12 trafficking protein uses glutathione transferase activity for processing alkylcobalamins (2009). https://pubmed.ncbi.nlm.nih.gov/19801555/ DOI: 10.1074/jbc.M109.057877
Complete structured claim and evidence
In the human MMACHC dealkylation study, cysteine and homocysteine did not substitute for glutathione as the thiol co-substrate.
GSH → MMACHC-catalyzed alkylcobalamin dealkylation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary abstract; indexed article Introduction/Figure 1
experimental_model
Purified human MMACHC thiol substitution assays
exposure
GSH versus cysteine or homocysteine
limitations
No implication that cysteine availability is irrelevant to cellular GSH synthesis; that upstream pathway was not tested here.
nutrient_topic
Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
organism
Homo sapiens
plain_language
Having a thiol group was not enough; the enzyme required glutathione in these assays.
primary_references
[kim-2009-gsh-dealkylation] A human vitamin B12 trafficking protein uses glutathione transferase activity for processing alkylcobalamins (2009). https://pubmed.ncbi.nlm.nih.gov/19801555/ DOI: 10.1074/jbc.M109.057877
tissue_or_cell_type
Cell-free assay
Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 739–751
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human MMACHC thiol substitution assays · source_derived_draft · unverified_draft
### b12-mmachc-thiol-specificity In the human MMACHC dealkylation study, cysteine and homocysteine did not substitute for glutathione as the thiol co-substrate. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Having a thiol group was not enough; the enzyme required glutathione in these assays. organism: Homo sapiens tissue_or_cell_type: Cell-free assay experimental_model: Purified human MMACHC thiol substitution assays limitations: No implication that cysteine availability is irrelevant to cellular GSH synthesis; that upstream pathway was not tested here. exposure: GSH versus cysteine or homocysteine cross_nutrient: true evidence_location: Primary abstract; indexed article Introduction/Figure 1 [kim-2009-gsh-dealkylation] A human vitamin B12 trafficking protein uses glutathione transferase activity for processing alkylcobalamins (2009). https://pubmed.ncbi.nlm.nih.gov/19801555/ DOI: 10.1074/jbc.M109.057877
Complete structured claim and evidence
Purified human CblC/MMACHC supported GSH-dependent decyanation of cyanocobalamin to cob(II)alamin efficiently under anaerobic conditions; the human reaction was oxygen-sensitive.
Human MMACHC / cobalamin-processing protein CblC → Cyanocobalamin source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Abstract; indexed primary Results summary
experimental_model
Purified human MMACHC; oxygen-controlled biochemical assay
exposure
GSH and specified B12 form under anaerobic versus aerobic conditions
limitations
Abstract-level extraction; stronger aerobic activity of the C. elegans enzyme must not be attributed to human MMACHC.
nutrient_topic
Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
organism
Homo sapiens
plain_language
Glutathione could supply reducing power, but oxygen strongly affected this human-protein reaction.
primary_references
[li-2014-gsh-electron] Glutathione-dependent one-electron transfer reactions catalyzed by a B12 trafficking protein (2014). https://pubmed.ncbi.nlm.nih.gov/24742678/ DOI: 10.1074/jbc.M114.567339
tissue_or_cell_type
Cell-free assay
Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 767–779
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human MMACHC; oxygen-controlled biochemical assay · source_derived_draft · unverified_draft
### b12-human-gsh-decyanation Purified human CblC/MMACHC supported GSH-dependent decyanation of cyanocobalamin to cob(II)alamin efficiently under anaerobic conditions; the human reaction was oxygen-sensitive. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione could supply reducing power, but oxygen strongly affected this human-protein reaction. organism: Homo sapiens tissue_or_cell_type: Cell-free assay experimental_model: Purified human MMACHC; oxygen-controlled biochemical assay limitations: Abstract-level extraction; stronger aerobic activity of the C. elegans enzyme must not be attributed to human MMACHC. exposure: GSH and specified B12 form under anaerobic versus aerobic conditions cross_nutrient: true evidence_location: Abstract; indexed primary Results summary [li-2014-gsh-electron] Glutathione-dependent one-electron transfer reactions catalyzed by a B12 trafficking protein (2014). https://pubmed.ncbi.nlm.nih.gov/24742678/ DOI: 10.1074/jbc.M114.567339
Complete structured claim and evidence
Purified human CblC/MMACHC supported GSH-dependent reduction of aquocobalamin to cob(II)alamin efficiently under anaerobic conditions; the human reaction was oxygen-sensitive.
Human MMACHC / cobalamin-processing protein CblC → Aquocobalamin source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Abstract; indexed primary Results summary
experimental_model
Purified human MMACHC; oxygen-controlled biochemical assay
exposure
GSH and specified B12 form under anaerobic versus aerobic conditions
limitations
Abstract-level extraction; stronger aerobic activity of the C. elegans enzyme must not be attributed to human MMACHC.
nutrient_topic
Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
organism
Homo sapiens
plain_language
Glutathione could supply reducing power, but oxygen strongly affected this human-protein reaction.
primary_references
[li-2014-gsh-electron] Glutathione-dependent one-electron transfer reactions catalyzed by a B12 trafficking protein (2014). https://pubmed.ncbi.nlm.nih.gov/24742678/ DOI: 10.1074/jbc.M114.567339
tissue_or_cell_type
Cell-free assay
Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 781–793
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human MMACHC; oxygen-controlled biochemical assay · source_derived_draft · unverified_draft
### b12-human-gsh-reduction Purified human CblC/MMACHC supported GSH-dependent reduction of aquocobalamin to cob(II)alamin efficiently under anaerobic conditions; the human reaction was oxygen-sensitive. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione could supply reducing power, but oxygen strongly affected this human-protein reaction. organism: Homo sapiens tissue_or_cell_type: Cell-free assay experimental_model: Purified human MMACHC; oxygen-controlled biochemical assay limitations: Abstract-level extraction; stronger aerobic activity of the C. elegans enzyme must not be attributed to human MMACHC. exposure: GSH and specified B12 form under anaerobic versus aerobic conditions cross_nutrient: true evidence_location: Abstract; indexed primary Results summary [li-2014-gsh-electron] Glutathione-dependent one-electron transfer reactions catalyzed by a B12 trafficking protein (2014). https://pubmed.ncbi.nlm.nih.gov/24742678/ DOI: 10.1074/jbc.M114.567339
Complete structured claim and evidence
GPX1 uses glutathione to remove hydrogen peroxide.
Classical GPX1 couples hydrogen-peroxide reduction to oxidation of reduced glutathione; water and glutathione disulfide are products.
GPX1 → Hydrogen peroxide source_derived_draftliterature_reviewed:supported_interpretation
Experimental context and source evidence
experimental_model
Animal selenium status and erythrocyte glutathione-peroxidase biochemistry.
limitations
This experiment-specific relationship does not establish a human dietary-deficiency threshold or supplementation benefit.
organism
Rat
Selenium: literature corrections and mechanism additions · lines 954–963
Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Animal selenium status and erythrocyte glutathione-peroxidase biochemistry. · secondary_verified · secondary_verified
## gpx1-peroxide-reduction GPX1 uses glutathione to remove hydrogen peroxide. Classical GPX1 couples hydrogen-peroxide reduction to oxidation of reduced glutathione; water and glutathione disulfide are products. Experimental model: Animal selenium status and erythrocyte glutathione-peroxidase biochemistry. Organism: Rat Limitations: This experiment-specific relationship does not establish a human dietary-deficiency threshold or supplementation benefit. Primary reference: [Selenium: biochemical role as a component of glutathione peroxidase](https://pubmed.ncbi.nlm.nih.gov/4686466/)
Complete structured claim and evidence
GPX2 can remove peroxide using glutathione.
Expressed human GPX2 exhibited glutathione-dependent hydrogen-peroxide reduction.
GPX2 → Hydrogen peroxide source_derived_draftliterature_reviewed:direct_experimental
Experimental context and source evidence
cell_type
MCF-7 transfectants
experimental_model
GPX2 cDNA expression and enzyme assays
limitations
Expression model; not an intestinal clinical outcome.
organism
human
Selenium: literature corrections and mechanism additions · lines 642–652
Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · GPX2 cDNA expression and enzyme assays · secondary_verified · secondary_verified
## gpx2-reduces-peroxide GPX2 can remove peroxide using glutathione. Expressed human GPX2 exhibited glutathione-dependent hydrogen-peroxide reduction. Organism: human Cell type: MCF-7 transfectants Experimental model: GPX2 cDNA expression and enzyme assays Limitations: Expression model; not an intestinal clinical outcome. Primary reference: [Expression, characterization, and tissue distribution of a new cellular selenium-dependent glutathione peroxidase, GSHPx-GI](https://pubmed.ncbi.nlm.nih.gov/8428933/)
Complete structured claim and evidence
GPX3 can remove peroxide outside cells.
Purified human plasma glutathione peroxidase reduced hydrogen peroxide using glutathione.
GPX3 → Hydrogen peroxide source_derived_draftliterature_reviewed:direct_experimental
Experimental context and source evidence
cell_type
plasma
experimental_model
Purified enzyme kinetics
limitations
Assay glutathione availability does not define every physiological electron donor.
organism
human
Selenium: literature corrections and mechanism additions · lines 678–688
Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Purified enzyme kinetics · secondary_verified · secondary_verified
## gpx3-reduces-extracellular-peroxide GPX3 can remove peroxide outside cells. Purified human plasma glutathione peroxidase reduced hydrogen peroxide using glutathione. Organism: human Cell type: plasma Experimental model: Purified enzyme kinetics Limitations: Assay glutathione availability does not define every physiological electron donor. Primary reference: [Characterization of the major hydroperoxide-reducing activity of human plasma. Purification and properties of a selenium-dependent glutathione peroxidase.](https://www.sciencedirect.com/science/article/pii/S0021925818453926)
Complete structured claim and evidence
Purified PHGPX (GPX4) with glutathione reduced phospholipid hydroperoxides within photooxidized human erythrocyte ghost membranes to alcohol products without prior phospholipase cleavage.
GPX4 → Phospholipid hydroperoxides source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary abstract
experimental_model
Rose-bengal photoperoxidation followed by enzyme treatment
exposure
GSH/PHGPX after photooxidation.
limitations
Purified-enzyme preparation; distinguishes peroxide removal from vitamin E radical trapping.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Human-derived cell-free membranes
plain_language
GPX4 removed peroxide groups from membrane phospholipids using glutathione.
primary_references
[ver-thomas1990] Protective action of phospholipid hydroperoxide glutathione peroxidase against membrane-damaging lipid peroxidation. In situ reduction of phospholipid and cholesterol hydroperoxides. (1990). https://pubmed.ncbi.nlm.nih.gov/2294113/ DOI: 10.1016/s0021-9258(19)40252-4
tissue_or_cell_type
Erythrocyte ghosts
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 550–562
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rose-bengal photoperoxidation followed by enzyme treatment · source_derived_draft · unverified_draft
### ver-gpx4-pl-hydroperoxide-reduction Purified PHGPX (GPX4) with glutathione reduced phospholipid hydroperoxides within photooxidized human erythrocyte ghost membranes to alcohol products without prior phospholipase cleavage. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: GPX4 removed peroxide groups from membrane phospholipids using glutathione. organism: Human-derived cell-free membranes tissue_or_cell_type: Erythrocyte ghosts experimental_model: Rose-bengal photoperoxidation followed by enzyme treatment limitations: Purified-enzyme preparation; distinguishes peroxide removal from vitamin E radical trapping. exposure: GSH/PHGPX after photooxidation. cross_nutrient: true evidence_location: Primary abstract [ver-thomas1990] Protective action of phospholipid hydroperoxide glutathione peroxidase against membrane-damaging lipid peroxidation. In situ reduction of phospholipid and cholesterol hydroperoxides. (1990). https://pubmed.ncbi.nlm.nih.gov/2294113/ DOI: 10.1016/s0021-9258(19)40252-4
Complete structured claim and evidence
Glutathione depletion in response to one class of ferroptosis inducers inactivated glutathione peroxidases, while another class directly inhibited GPX4.
GSH → GPX4 source_derived_draftungraded
Experimental context and source evidence
evidence_span
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experimental_model
Metabolomics, chemoproteomics, perturbation and cancer-cell sensitivity profiling
exposure
Two classes of ferroptosis-inducing compounds
limitations
Preclinical drug-response mechanism; selenium or vitamin E supplementation is not established as a universal treatment.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Human cancer-cell lines and mouse xenografts
plain_language
Losing the antioxidant substrate and directly blocking its enzyme are different routes into the same vulnerability.
primary_references
[iron-p24439385] Regulation of ferroptotic cancer cell death by GPX4. (2014). https://pubmed.ncbi.nlm.nih.gov/24439385/ DOI: 10.1016/j.cell.2013.12.010
tissue_or_cell_type
Glutathione/GPX4 antioxidant system
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1252–1263
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Metabolomics, chemoproteomics, perturbation and cancer-cell sensitivity profiling · source_derived_draft · unverified_draft
### iron-gsh-gpx-loss Glutathione depletion in response to one class of ferroptosis inducers inactivated glutathione peroxidases, while another class directly inhibited GPX4. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: Losing the antioxidant substrate and directly blocking its enzyme are different routes into the same vulnerability. organism: Human cancer-cell lines and mouse xenografts tissue_or_cell_type: Glutathione/GPX4 antioxidant system experimental_model: Metabolomics, chemoproteomics, perturbation and cancer-cell sensitivity profiling limitations: Preclinical drug-response mechanism; selenium or vitamin E supplementation is not established as a universal treatment. exposure: Two classes of ferroptosis-inducing compounds evidence_span: {"source_cache": "artifacts/iron-research/24439385.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8d588af38ec5438fbec80971ead0764466237b3382492051aa3b3c297841703", "start_char": 0, "end_char": 957, "text_sha256": "f8d588af38ec5438fbec80971ead0764466237b3382492051aa3b3c297841703"} [iron-p24439385] Regulation of ferroptotic cancer cell death by GPX4. (2014). https://pubmed.ncbi.nlm.nih.gov/24439385/ DOI: 10.1016/j.cell.2013.12.010
Complete structured claim and evidence
GPX4 overexpression or knockdown altered lethality of all 12 tested ferroptosis inducers, but not 11 compounds with other lethal mechanisms.
GPX4 → Ferroptosis source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/iron-research/24439385.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8d588af38ec5438fbec80971ead0764466237b3382492051aa3b3c297841703", "start_char": 0, "end_char": 957, "text_sha256": "f8d588af38ec5438fbec80971ead0764466237b3382492051aa3b3c297841703"}
experimental_model
Metabolomics, chemoproteomics, perturbation and cancer-cell sensitivity profiling
exposure
Two classes of ferroptosis-inducing compounds
limitations
Preclinical drug-response mechanism; selenium or vitamin E supplementation is not established as a universal treatment.
nutrient_topic
Iron research collection; topical membership is not evidence of a direct dietary effect. · Iron
organism
Human cancer-cell lines and mouse xenografts
plain_language
The protective enzyme specifically controlled this iron-linked death pathway in the tested cells.
primary_references
[iron-p24439385] Regulation of ferroptotic cancer cell death by GPX4. (2014). https://pubmed.ncbi.nlm.nih.gov/24439385/ DOI: 10.1016/j.cell.2013.12.010
tissue_or_cell_type
Glutathione/GPX4 antioxidant system
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17) · lines 1265–1276
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Metabolomics, chemoproteomics, perturbation and cancer-cell sensitivity profiling · source_derived_draft · unverified_draft
### iron-gpx4-ferroptosis GPX4 overexpression or knockdown altered lethality of all 12 tested ferroptosis inducers, but not 11 compounds with other lethal mechanisms. Condition category: normal nutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect. plain_language: The protective enzyme specifically controlled this iron-linked death pathway in the tested cells. organism: Human cancer-cell lines and mouse xenografts tissue_or_cell_type: Glutathione/GPX4 antioxidant system experimental_model: Metabolomics, chemoproteomics, perturbation and cancer-cell sensitivity profiling limitations: Preclinical drug-response mechanism; selenium or vitamin E supplementation is not established as a universal treatment. exposure: Two classes of ferroptosis-inducing compounds evidence_span: {"source_cache": "artifacts/iron-research/24439385.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f8d588af38ec5438fbec80971ead0764466237b3382492051aa3b3c297841703", "start_char": 0, "end_char": 957, "text_sha256": "f8d588af38ec5438fbec80971ead0764466237b3382492051aa3b3c297841703"} [iron-p24439385] Regulation of ferroptotic cancer cell death by GPX4. (2014). https://pubmed.ncbi.nlm.nih.gov/24439385/ DOI: 10.1016/j.cell.2013.12.010
Complete structured claim and evidence
Added glutathione failed to protect hemoglobin during oxidant challenge of selenium-deficient rat hemolyzates with very low glutathione-peroxidase activity.
GSH → Hemoglobin oxidative damage source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
Explains why B2-dependent GSH recycling and selenium-dependent GSH use are distinct requirements.
evidence_location
Abstract
experimental_model
Erythrocyte hemolyzates from selenium-deficient rats; glutathione addition during peroxide/ascorbate challenge and 75Se enzyme purification.
exposure
Selenium-deficient diet, then ex-vivo oxidant and glutathione exposure
limitations
Separate from FAD-dependent GSR recycling; neither riboflavin nor combined nutrient repletion was tested.
nutrient_topic
Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
organism
Rattus norvegicus
plain_language
Supplying glutathione did not replace the missing selenium-dependent enzyme activity.
primary_references
[rotruck1973] Selenium: biochemical role as a component of glutathione peroxidase. (1973). https://pubmed.ncbi.nlm.nih.gov/4686466/ DOI: 10.1126/science.179.4073.588
tissue_or_cell_type
Erythrocyte hemolyzates
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1472–1484
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Erythrocyte hemolyzates from selenium-deficient rats; glutathione addition during peroxide/ascorbate challenge and 75Se enzyme purification. · source_derived_draft · unverified_draft
### b2-redox-gsh-needs-selenium-peroxidase Added glutathione failed to protect hemoglobin during oxidant challenge of selenium-deficient rat hemolyzates with very low glutathione-peroxidase activity. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: Supplying glutathione did not replace the missing selenium-dependent enzyme activity. organism: Rattus norvegicus tissue_or_cell_type: Erythrocyte hemolyzates experimental_model: Erythrocyte hemolyzates from selenium-deficient rats; glutathione addition during peroxide/ascorbate challenge and 75Se enzyme purification. limitations: Separate from FAD-dependent GSR recycling; neither riboflavin nor combined nutrient repletion was tested. exposure: Selenium-deficient diet, then ex-vivo oxidant and glutathione exposure cross_nutrient: Explains why B2-dependent GSH recycling and selenium-dependent GSH use are distinct requirements. evidence_location: Abstract [rotruck1973] Selenium: biochemical role as a component of glutathione peroxidase. (1973). https://pubmed.ncbi.nlm.nih.gov/4686466/ DOI: 10.1126/science.179.4073.588
Complete structured claim and evidence
Purified human placental glutaredoxin catalyzed GSH-dependent reduction of DHA to ascorbate.
Human glutaredoxin 1 / GLRX → Dehydroascorbic acid source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Purified human placental glutaredoxin and bovine liver PDI; additional porcine/bovine glutaredoxins
exposure
Purified enzyme plus DHA and GSH
limitations
In vitro activity does not establish its share of total placental recycling.
nutrient_topic
Vitamin C research collection; topical membership is not evidence of a direct dietary effect. · Vitamin C
organism
Homo sapiens
plain_language
Glutaredoxin can use glutathione to restore reduced vitamin C.
primary_references
[wells1990] Mammalian thioltransferase (glutaredoxin) and protein disulfide isomerase have dehydroascorbate reductase activity. (1990). https://pubmed.ncbi.nlm.nih.gov/2394726/ DOI: 10.1016/s0021-9258(18)55401-6
tissue_or_cell_type
Placental enzyme preparation
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 351–362
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human placental glutaredoxin and bovine liver PDI; additional porcine/bovine glutaredoxins · source_derived_draft · unverified_draft
### vc-transport-human-glutaredoxin-dha Purified human placental glutaredoxin catalyzed GSH-dependent reduction of DHA to ascorbate. Condition category: normal nutrient_topic: Vitamin C research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutaredoxin can use glutathione to restore reduced vitamin C. organism: Homo sapiens tissue_or_cell_type: Placental enzyme preparation experimental_model: Purified human placental glutaredoxin and bovine liver PDI; additional porcine/bovine glutaredoxins limitations: In vitro activity does not establish its share of total placental recycling. exposure: Purified enzyme plus DHA and GSH cross_nutrient: true [wells1990] Mammalian thioltransferase (glutaredoxin) and protein disulfide isomerase have dehydroascorbate reductase activity. (1990). https://pubmed.ncbi.nlm.nih.gov/2394726/ DOI: 10.1016/s0021-9258(18)55401-6
Complete structured claim and evidence
At a physiological vitamin E-to-phospholipid ratio, inhibition of iron-dependent lipid peroxidation in rat liver microsomes and dispersed microsomal lipids was observed only when PHGPX (GPX4) and glutathione were also present.
Alpha-tocopherol → Lipid peroxidation source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
evidence_location
Primary abstract
experimental_model
Microsomes and Triton-dispersed lipid micelles
exposure
Iron-dependent peroxidation; physiological vitamin E:phospholipid ratio as reported in abstract.
limitations
Exact concentrations are not available in the inspected abstract. Model-specific dependence does not imply every membrane requires added GPX4 to show E protection.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Rattus norvegicus
plain_language
Vitamin E protection depended on peroxide removal by the GPX4/glutathione system in these preparations.
primary_references
[ver-maiorino1989] Microsomal lipid peroxidation: effect of vitamin E and its functional interaction with phospholipid hydroperoxide glutathione peroxidase. (1989). https://pubmed.ncbi.nlm.nih.gov/2586229/ DOI: 10.1007/bf02535211
tissue_or_cell_type
Liver microsomal lipids
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 592–604
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Microsomes and Triton-dispersed lipid micelles · source_derived_draft · unverified_draft
### ver-gpx4-gsh-tocopherol-cooperation At a physiological vitamin E-to-phospholipid ratio, inhibition of iron-dependent lipid peroxidation in rat liver microsomes and dispersed microsomal lipids was observed only when PHGPX (GPX4) and glutathione were also present. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin E protection depended on peroxide removal by the GPX4/glutathione system in these preparations. organism: Rattus norvegicus tissue_or_cell_type: Liver microsomal lipids experimental_model: Microsomes and Triton-dispersed lipid micelles limitations: Exact concentrations are not available in the inspected abstract. Model-specific dependence does not imply every membrane requires added GPX4 to show E protection. exposure: Iron-dependent peroxidation; physiological vitamin E:phospholipid ratio as reported in abstract. cross_nutrient: true evidence_location: Primary abstract [ver-maiorino1989] Microsomal lipid peroxidation: effect of vitamin E and its functional interaction with phospholipid hydroperoxide glutathione peroxidase. (1989). https://pubmed.ncbi.nlm.nih.gov/2586229/ DOI: 10.1007/bf02535211
Complete structured claim and evidence
Six weeks of vitamin E-depleted diet before inducible endothelial Gpx4 deletion led to endothelial detachment and cell death in multiple mouse organs, accompanied by thrombosis and approximately 80% knockout mortality.
Endothelium-directed GPX4 loss → Endothelial cell death source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Primary abstract
experimental_model
Combined dietary depletion and 4-hydroxytamoxifen-induced deletion
exposure
Six-week vitamin E depletion preceding Gpx4 deletion.
limitations
Primary abstract only; vascular and survival endpoints in one mouse deletion model, not general human deficiency or dosing evidence.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Mus musculus
plain_language
Removing dietary vitamin E exposed severe vascular injury in mice whose endothelial GPX4 was then deleted.
primary_references
[ver-wortmann2013] Combined deficiency in glutathione peroxidase 4 and vitamin E causes multiorgan thrombus formation and early death in mice. (2013). https://pubmed.ncbi.nlm.nih.gov/23770613/ DOI: 10.1161/circresaha.113.279984
tissue_or_cell_type
Multiorgan vascular endothelium
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 648–660
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Combined dietary depletion and 4-hydroxytamoxifen-induced deletion · source_derived_draft · unverified_draft
### ver-endo-combined-e-gpx4-loss Six weeks of vitamin E-depleted diet before inducible endothelial Gpx4 deletion led to endothelial detachment and cell death in multiple mouse organs, accompanied by thrombosis and approximately 80% knockout mortality. Condition category: nutrient_deficiency nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Removing dietary vitamin E exposed severe vascular injury in mice whose endothelial GPX4 was then deleted. organism: Mus musculus tissue_or_cell_type: Multiorgan vascular endothelium experimental_model: Combined dietary depletion and 4-hydroxytamoxifen-induced deletion limitations: Primary abstract only; vascular and survival endpoints in one mouse deletion model, not general human deficiency or dosing evidence. exposure: Six-week vitamin E depletion preceding Gpx4 deletion. cross_nutrient: true evidence_location: Primary abstract [ver-wortmann2013] Combined deficiency in glutathione peroxidase 4 and vitamin E causes multiorgan thrombus formation and early death in mice. (2013). https://pubmed.ncbi.nlm.nih.gov/23770613/ DOI: 10.1161/circresaha.113.279984
Complete structured claim and evidence
Endothelium-specific Gpx4 deletion produced no obvious impairment of vascular homeostasis in mice maintained on a normal diet in the reported study.
Endothelium-directed GPX4 loss → Vascular homeostasis source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Primary abstract
experimental_model
Endothelial Gpx4 conditional deletion
exposure
Normal diet; no quantitative vitamin E content assigned from abstract.
limitations
Primary abstract only; vascular and survival endpoints in one mouse deletion model, not general human deficiency or dosing evidence.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Mus musculus
plain_language
Loss of endothelial GPX4 alone did not produce an obvious vascular phenotype under the normal-diet conditions tested.
primary_references
[ver-wortmann2013] Combined deficiency in glutathione peroxidase 4 and vitamin E causes multiorgan thrombus formation and early death in mice. (2013). https://pubmed.ncbi.nlm.nih.gov/23770613/ DOI: 10.1161/circresaha.113.279984
tissue_or_cell_type
Vascular endothelium
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 634–646
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Endothelial Gpx4 conditional deletion · source_derived_draft · unverified_draft
### ver-endo-gpx4-normal-diet Endothelium-specific Gpx4 deletion produced no obvious impairment of vascular homeostasis in mice maintained on a normal diet in the reported study. Condition category: machinery_impairment nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Loss of endothelial GPX4 alone did not produce an obvious vascular phenotype under the normal-diet conditions tested. organism: Mus musculus tissue_or_cell_type: Vascular endothelium experimental_model: Endothelial Gpx4 conditional deletion limitations: Primary abstract only; vascular and survival endpoints in one mouse deletion model, not general human deficiency or dosing evidence. exposure: Normal diet; no quantitative vitamin E content assigned from abstract. cross_nutrient: true evidence_location: Primary abstract [ver-wortmann2013] Combined deficiency in glutathione peroxidase 4 and vitamin E causes multiorgan thrombus formation and early death in mice. (2013). https://pubmed.ncbi.nlm.nih.gov/23770613/ DOI: 10.1161/circresaha.113.279984
Complete structured claim and evidence
Maternal dietary supplementation with 500 IU/kg DL-alpha-tocopheryl acetate through gestation and nursing allowed Alb-Cre;Gpx4fl/fl pups to survive to weaning, whereas liver-specific Gpx4-null pups on standard chow died within 48 hours after birth.
All-rac-alpha-tocopheryl acetate → Hepatocyte-directed GPX4 loss source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Results/Table 2; standard-chow comparison Table 1
experimental_model
Alb-Cre conditional Gpx4 deletion and maternal diet
exposure
500 IU/kg DL-alpha-tocopheryl acetate during gestation/lactation; weaning at 3 weeks.
limitations
Alb-Cre Gpx4 loss is machinery impairment, not selenium deficiency; mouse survival rescue does not establish human substitutability.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Mus musculus
plain_language
Extra dietary vitamin E rescued early survival in mice lacking liver GPX4.
primary_references
[ver-carlson2016] Glutathione peroxidase 4 and vitamin E cooperatively prevent hepatocellular degeneration. (2016). https://pubmed.ncbi.nlm.nih.gov/27262435/ DOI: 10.1016/j.redox.2016.05.003
tissue_or_cell_type
Hepatocytes and whole-animal survival
trigger_kind
machinery_impairment Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 606–618
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Alb-Cre conditional Gpx4 deletion and maternal diet · source_derived_draft · unverified_draft
### ver-liver-gpx4-e-rescue Maternal dietary supplementation with 500 IU/kg DL-alpha-tocopheryl acetate through gestation and nursing allowed Alb-Cre;Gpx4fl/fl pups to survive to weaning, whereas liver-specific Gpx4-null pups on standard chow died within 48 hours after birth. Condition category: machinery_impairment nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Extra dietary vitamin E rescued early survival in mice lacking liver GPX4. organism: Mus musculus tissue_or_cell_type: Hepatocytes and whole-animal survival experimental_model: Alb-Cre conditional Gpx4 deletion and maternal diet limitations: Alb-Cre Gpx4 loss is machinery impairment, not selenium deficiency; mouse survival rescue does not establish human substitutability. exposure: 500 IU/kg DL-alpha-tocopheryl acetate during gestation/lactation; weaning at 3 weeks. cross_nutrient: true evidence_location: Results/Table 2; standard-chow comparison Table 1 [ver-carlson2016] Glutathione peroxidase 4 and vitamin E cooperatively prevent hepatocellular degeneration. (2016). https://pubmed.ncbi.nlm.nih.gov/27262435/ DOI: 10.1016/j.redox.2016.05.003
Complete structured claim and evidence
After six weeks on vitamin E-enriched diets, switching liver-specific Gpx4-null mice to vitamin E-deficient diet caused extensive hepatocellular necrosis and loss of the prior survival rescue; control genotypes survived the monitored 78 days after withdrawal.
Hepatocyte-directed GPX4 loss → Hepatocyte necrosis source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
cross_nutrient
true
evidence_location
Figures 4–5
experimental_model
Diet withdrawal after developmental rescue
exposure
E-enriched diet through 6 weeks; subsequent E withdrawal; necrosis examined after 3 weeks.
limitations
Alb-Cre Gpx4 loss is machinery impairment, not selenium deficiency; mouse survival rescue does not establish human substitutability.
nutrient_topic
Vitamin E research collection; topical membership is not evidence of a direct dietary effect. · Vitamin E
organism
Mus musculus
plain_language
The rescued mice remained dependent on continued vitamin E supply.
primary_references
[ver-carlson2016] Glutathione peroxidase 4 and vitamin E cooperatively prevent hepatocellular degeneration. (2016). https://pubmed.ncbi.nlm.nih.gov/27262435/ DOI: 10.1016/j.redox.2016.05.003
tissue_or_cell_type
Liver
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 620–632
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Diet withdrawal after developmental rescue · source_derived_draft · unverified_draft
### ver-liver-gpx4-e-withdrawal After six weeks on vitamin E-enriched diets, switching liver-specific Gpx4-null mice to vitamin E-deficient diet caused extensive hepatocellular necrosis and loss of the prior survival rescue; control genotypes survived the monitored 78 days after withdrawal. Condition category: nutrient_deficiency nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: The rescued mice remained dependent on continued vitamin E supply. organism: Mus musculus tissue_or_cell_type: Liver experimental_model: Diet withdrawal after developmental rescue limitations: Alb-Cre Gpx4 loss is machinery impairment, not selenium deficiency; mouse survival rescue does not establish human substitutability. exposure: E-enriched diet through 6 weeks; subsequent E withdrawal; necrosis examined after 3 weeks. cross_nutrient: true evidence_location: Figures 4–5 [ver-carlson2016] Glutathione peroxidase 4 and vitamin E cooperatively prevent hepatocellular degeneration. (2016). https://pubmed.ncbi.nlm.nih.gov/27262435/ DOI: 10.1016/j.redox.2016.05.003
Complete structured claim and evidence
Sulforaphane underwent both nonenzymatic and GST-catalyzed conjugation with glutathione.
GSH → Sulforaphane / SFN, stereochemistry specified per study source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/sulforaphane-research/7826396.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5dee3c3a8c8069c33fac2653f16f3521cdd17ef5e8ebddd0f82cfa3a5c95c0fe", "start_char": 0, "end_char": 989, "text_sha256": "5dee3c3a8c8069c33fac2653f16f3521cdd17ef5e8ebddd0f82cfa3a5c95c0fe"}
experimental_model
Recombinant human GST conjugation and reverse-reaction kinetics
exposure
Four isothiocyanates and GSTP1-1, GSTM1-1, GSTA1-1 and GSTM2-2
limitations
Relative enzyme rates are not whole-person clearance predictions; reverse reactions were slower and inhibited by high GSH.
nutrient_topic
Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study
organism
Human GST isoenzymes
plain_language
Glutathione is a reacting molecule here, not merely an antioxidant label.
primary_references
[sulforaphane-p7826396] Reversible conjugation of isothiocyanates with glutathione catalyzed by human glutathione transferases. (1995). https://pubmed.ncbi.nlm.nih.gov/7826396/ DOI: 10.1006/bbrc.1995.1106
tissue_or_cell_type
Isothiocyanate-glutathione chemistry
Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 281–292
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human GST conjugation and reverse-reaction kinetics · source_derived_draft · unverified_draft
### sulforaphane-gsh-conjugation Sulforaphane underwent both nonenzymatic and GST-catalyzed conjugation with glutathione. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione is a reacting molecule here, not merely an antioxidant label. organism: Human GST isoenzymes tissue_or_cell_type: Isothiocyanate-glutathione chemistry experimental_model: Recombinant human GST conjugation and reverse-reaction kinetics limitations: Relative enzyme rates are not whole-person clearance predictions; reverse reactions were slower and inhibited by high GSH. exposure: Four isothiocyanates and GSTP1-1, GSTM1-1, GSTA1-1 and GSTM2-2 evidence_span: {"source_cache": "artifacts/sulforaphane-research/7826396.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5dee3c3a8c8069c33fac2653f16f3521cdd17ef5e8ebddd0f82cfa3a5c95c0fe", "start_char": 0, "end_char": 989, "text_sha256": "5dee3c3a8c8069c33fac2653f16f3521cdd17ef5e8ebddd0f82cfa3a5c95c0fe"} [sulforaphane-p7826396] Reversible conjugation of isothiocyanates with glutathione catalyzed by human glutathione transferases. (1995). https://pubmed.ncbi.nlm.nih.gov/7826396/ DOI: 10.1006/bbrc.1995.1106
Complete structured claim and evidence
GSTM1-1 was among the efficient tested human GST catalysts for isothiocyanate conjugation.
Human glutathione S-transferase M1 → Sulforaphane-glutathione conjugate / SFN-GSH source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/sulforaphane-research/7826396.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5dee3c3a8c8069c33fac2653f16f3521cdd17ef5e8ebddd0f82cfa3a5c95c0fe", "start_char": 0, "end_char": 989, "text_sha256": "5dee3c3a8c8069c33fac2653f16f3521cdd17ef5e8ebddd0f82cfa3a5c95c0fe"}
experimental_model
Recombinant human GST conjugation and reverse-reaction kinetics
exposure
Four isothiocyanates and GSTP1-1, GSTM1-1, GSTA1-1 and GSTM2-2
limitations
Relative enzyme rates are not whole-person clearance predictions; reverse reactions were slower and inhibited by high GSH.
nutrient_topic
Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study
organism
Human GST isoenzymes
plain_language
Different GST isoenzymes can participate in this route.
primary_references
[sulforaphane-p7826396] Reversible conjugation of isothiocyanates with glutathione catalyzed by human glutathione transferases. (1995). https://pubmed.ncbi.nlm.nih.gov/7826396/ DOI: 10.1006/bbrc.1995.1106
tissue_or_cell_type
Isothiocyanate-glutathione chemistry
Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 268–279
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human GST conjugation and reverse-reaction kinetics · source_derived_draft · unverified_draft
### sulforaphane-gstm-conjugation GSTM1-1 was among the efficient tested human GST catalysts for isothiocyanate conjugation. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: Different GST isoenzymes can participate in this route. organism: Human GST isoenzymes tissue_or_cell_type: Isothiocyanate-glutathione chemistry experimental_model: Recombinant human GST conjugation and reverse-reaction kinetics limitations: Relative enzyme rates are not whole-person clearance predictions; reverse reactions were slower and inhibited by high GSH. exposure: Four isothiocyanates and GSTP1-1, GSTM1-1, GSTA1-1 and GSTM2-2 evidence_span: {"source_cache": "artifacts/sulforaphane-research/7826396.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5dee3c3a8c8069c33fac2653f16f3521cdd17ef5e8ebddd0f82cfa3a5c95c0fe", "start_char": 0, "end_char": 989, "text_sha256": "5dee3c3a8c8069c33fac2653f16f3521cdd17ef5e8ebddd0f82cfa3a5c95c0fe"} [sulforaphane-p7826396] Reversible conjugation of isothiocyanates with glutathione catalyzed by human glutathione transferases. (1995). https://pubmed.ncbi.nlm.nih.gov/7826396/ DOI: 10.1006/bbrc.1995.1106
Complete structured claim and evidence
GSTP1-1 catalyzed sulforaphane conjugation with glutathione in the human enzyme comparison.
Human glutathione S-transferase P1 / GSTP1 → Sulforaphane-glutathione conjugate / SFN-GSH source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/sulforaphane-research/7826396.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5dee3c3a8c8069c33fac2653f16f3521cdd17ef5e8ebddd0f82cfa3a5c95c0fe", "start_char": 0, "end_char": 989, "text_sha256": "5dee3c3a8c8069c33fac2653f16f3521cdd17ef5e8ebddd0f82cfa3a5c95c0fe"}
experimental_model
Recombinant human GST conjugation and reverse-reaction kinetics
exposure
Four isothiocyanates and GSTP1-1, GSTM1-1, GSTA1-1 and GSTM2-2
limitations
Relative enzyme rates are not whole-person clearance predictions; reverse reactions were slower and inhibited by high GSH.
nutrient_topic
Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study
organism
Human GST isoenzymes
plain_language
Glutathione attaches to sulforaphane during its handling.
primary_references
[sulforaphane-p7826396] Reversible conjugation of isothiocyanates with glutathione catalyzed by human glutathione transferases. (1995). https://pubmed.ncbi.nlm.nih.gov/7826396/ DOI: 10.1006/bbrc.1995.1106
tissue_or_cell_type
Isothiocyanate-glutathione chemistry
Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 255–266
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human GST conjugation and reverse-reaction kinetics · source_derived_draft · unverified_draft
### sulforaphane-gstp-conjugation GSTP1-1 catalyzed sulforaphane conjugation with glutathione in the human enzyme comparison. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione attaches to sulforaphane during its handling. organism: Human GST isoenzymes tissue_or_cell_type: Isothiocyanate-glutathione chemistry experimental_model: Recombinant human GST conjugation and reverse-reaction kinetics limitations: Relative enzyme rates are not whole-person clearance predictions; reverse reactions were slower and inhibited by high GSH. exposure: Four isothiocyanates and GSTP1-1, GSTM1-1, GSTA1-1 and GSTM2-2 evidence_span: {"source_cache": "artifacts/sulforaphane-research/7826396.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5dee3c3a8c8069c33fac2653f16f3521cdd17ef5e8ebddd0f82cfa3a5c95c0fe", "start_char": 0, "end_char": 989, "text_sha256": "5dee3c3a8c8069c33fac2653f16f3521cdd17ef5e8ebddd0f82cfa3a5c95c0fe"} [sulforaphane-p7826396] Reversible conjugation of isothiocyanates with glutathione catalyzed by human glutathione transferases. (1995). https://pubmed.ncbi.nlm.nih.gov/7826396/ DOI: 10.1006/bbrc.1995.1106
Complete structured claim and evidence
MRP1-overexpressing human cells supported rapid export of accumulated sulforaphane, mainly as its glutathione conjugate.
Human multidrug resistance-associated protein 1 / ABCC1 / MRP1 → Sulforaphane/glutathione-conjugate efflux source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/sulforaphane-research/11988104.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5759bc0af52a1e906602549a3920ebba5641d09b63cc87f0dc61ea8efcb724a9", "start_char": 0, "end_char": 1567, "text_sha256": "5759bc0af52a1e906602549a3920ebba5641d09b63cc87f0dc61ea8efcb724a9"}
experimental_model
Transporter-overexpression and temperature/inhibitor experiments
exposure
Sulforaphane loading; ABCC1 or ABCB1 expression
limitations
Cancer-cell transport experiments; not a measured clinical drug interaction.
nutrient_topic
Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study
organism
Human HL60 leukemia and 8226 myeloma cells
plain_language
A transporter can shorten intracellular exposure.
primary_references
[sulforaphane-p11988104] High cellular accumulation of sulphoraphane, a dietary anticarcinogen, is followed by rapid transporter-mediated export as a glutathione conjugate. (2002). https://pubmed.ncbi.nlm.nih.gov/11988104/ DOI: 10.1042/bj3640301
tissue_or_cell_type
Intracellular retention and export
Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 307–318
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transporter-overexpression and temperature/inhibitor experiments · source_derived_draft · unverified_draft
### sulforaphane-abcc1-efflux MRP1-overexpressing human cells supported rapid export of accumulated sulforaphane, mainly as its glutathione conjugate. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: A transporter can shorten intracellular exposure. organism: Human HL60 leukemia and 8226 myeloma cells tissue_or_cell_type: Intracellular retention and export experimental_model: Transporter-overexpression and temperature/inhibitor experiments limitations: Cancer-cell transport experiments; not a measured clinical drug interaction. exposure: Sulforaphane loading; ABCC1 or ABCB1 expression evidence_span: {"source_cache": "artifacts/sulforaphane-research/11988104.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5759bc0af52a1e906602549a3920ebba5641d09b63cc87f0dc61ea8efcb724a9", "start_char": 0, "end_char": 1567, "text_sha256": "5759bc0af52a1e906602549a3920ebba5641d09b63cc87f0dc61ea8efcb724a9"} [sulforaphane-p11988104] High cellular accumulation of sulphoraphane, a dietary anticarcinogen, is followed by rapid transporter-mediated export as a glutathione conjugate. (2002). https://pubmed.ncbi.nlm.nih.gov/11988104/ DOI: 10.1042/bj3640301
Complete structured claim and evidence
Sulforaphane increased GCLM gene expression in early-passage nonsenescent MRC-5 fibroblasts.
Sulforaphane / SFN, stereochemistry specified per study → Human glutamate-cysteine ligase modifier subunit / GCLM source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/sulforaphane-research/30595796.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "13f25a5ca61ca9bdf80d4b24878682c90b414a5718a73b6a5b86ff20a9673279", "start_char": 14986, "end_char": 15205, "text_sha256": "c8a5b844826129e5cff61e4e19c0eb34f04a29a8feb8ced52a567eae1585d935"}
experimental_model
Replicative culture and metabolic/gene-expression measurements
exposure
Sulforaphane treatment during serial culture
limitations
Cell-culture senescence is not human longevity; expression is not necessarily flux.
nutrient_topic
Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study
organism
Human MRC-5 and BJ fibroblasts
plain_language
The response includes this separately identified defense-system protein.
primary_references
[sulforaphane-p30595796] Sulforaphane Delays Fibroblast Senescence by Curbing Cellular Glucose Uptake, Increased Glycolysis, and Oxidative Damage. (2018). https://pubmed.ncbi.nlm.nih.gov/30595796/ DOI: 10.1155/2018/5642148
tissue_or_cell_type
Glucose handling, antioxidant response and senescence
Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 931–942
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Replicative culture and metabolic/gene-expression measurements · source_derived_draft · unverified_draft
### sulforaphane-gclm-induction Sulforaphane increased GCLM gene expression in early-passage nonsenescent MRC-5 fibroblasts. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: The response includes this separately identified defense-system protein. organism: Human MRC-5 and BJ fibroblasts tissue_or_cell_type: Glucose handling, antioxidant response and senescence experimental_model: Replicative culture and metabolic/gene-expression measurements limitations: Cell-culture senescence is not human longevity; expression is not necessarily flux. exposure: Sulforaphane treatment during serial culture evidence_span: {"source_cache": "artifacts/sulforaphane-research/30595796.fulltext.txt", "locator": "Primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "13f25a5ca61ca9bdf80d4b24878682c90b414a5718a73b6a5b86ff20a9673279", "start_char": 14986, "end_char": 15205, "text_sha256": "c8a5b844826129e5cff61e4e19c0eb34f04a29a8feb8ced52a567eae1585d935"} [sulforaphane-p30595796] Sulforaphane Delays Fibroblast Senescence by Curbing Cellular Glucose Uptake, Increased Glycolysis, and Oxidative Damage. (2018). https://pubmed.ncbi.nlm.nih.gov/30595796/ DOI: 10.1155/2018/5642148
Complete structured claim and evidence
Sulforaphane increased G6PD expression in the fibroblast study.
Sulforaphane / SFN, stereochemistry specified per study → Glucose-6-phosphate dehydrogenase / G6PD source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/sulforaphane-research/30595796.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "aa7d5e0ef15224906eb42eb49309439c966c30310740dbdea9553b76b2f91274", "start_char": 0, "end_char": 2097, "text_sha256": "aa7d5e0ef15224906eb42eb49309439c966c30310740dbdea9553b76b2f91274"}
experimental_model
Replicative culture and metabolic/gene-expression measurements
exposure
Sulforaphane treatment during serial culture
limitations
Cell-culture senescence is not human longevity; expression is not necessarily flux.
nutrient_topic
Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. · Sulforaphane / SFN, stereochemistry specified per study
organism
Human MRC-5 and BJ fibroblasts
plain_language
The response includes machinery connected to the cellular reducing-power supply.
primary_references
[sulforaphane-p30595796] Sulforaphane Delays Fibroblast Senescence by Curbing Cellular Glucose Uptake, Increased Glycolysis, and Oxidative Damage. (2018). https://pubmed.ncbi.nlm.nih.gov/30595796/ DOI: 10.1155/2018/5642148
tissue_or_cell_type
Glucose handling, antioxidant response and senescence
Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17) · lines 879–890
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Replicative culture and metabolic/gene-expression measurements · source_derived_draft · unverified_draft
### sulforaphane-g6pd-expression Sulforaphane increased G6PD expression in the fibroblast study. Condition category: normal nutrient_topic: Sulforaphane research collection; topical membership is not evidence of a direct dietary effect. plain_language: The response includes machinery connected to the cellular reducing-power supply. organism: Human MRC-5 and BJ fibroblasts tissue_or_cell_type: Glucose handling, antioxidant response and senescence experimental_model: Replicative culture and metabolic/gene-expression measurements limitations: Cell-culture senescence is not human longevity; expression is not necessarily flux. exposure: Sulforaphane treatment during serial culture evidence_span: {"source_cache": "artifacts/sulforaphane-research/30595796.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "aa7d5e0ef15224906eb42eb49309439c966c30310740dbdea9553b76b2f91274", "start_char": 0, "end_char": 2097, "text_sha256": "aa7d5e0ef15224906eb42eb49309439c966c30310740dbdea9553b76b2f91274"} [sulforaphane-p30595796] Sulforaphane Delays Fibroblast Senescence by Curbing Cellular Glucose Uptake, Increased Glycolysis, and Oxidative Damage. (2018). https://pubmed.ncbi.nlm.nih.gov/30595796/ DOI: 10.1155/2018/5642148
Complete structured claim and evidence
Genetic depletion of PC in human islets reduced glutathione and the GSH/GSSG ratio under nitrosative stress.
Human pyruvate carboxylase / PC → Human pancreatic-islet glutathione synthesis source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/biotin-research/34818536.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "48bcb3951c9b630862fdda839e0a54b80abe9e2cf2e79d0bfb7547e2af317523", "start_char": 35800, "end_char": 36138, "text_sha256": "b1dd7e5022ba64d19114d853d2f75c43e061cdca76e1938e95c19379e96c3933"}
experimental_model
Primary human-islet tracer metabolomics and PC knockdown under inflammatory/nitrosative stress
exposure
Glucose tracer, PC knockdown and nitric-oxide donor exposure
limitations
Genetic perturbation of PC in isolated islets is not dietary biotin depletion or evidence that biotin supplements raise glutathione in replete people.
nutrient_topic
Biotin research collection; topical membership is not evidence of a direct dietary effect. · Biotin
organism
Homo sapiens
plain_language
PC connects carbon metabolism to the cell’s ability to maintain glutathione.
primary_references
[b7-p34818536] Glucose metabolism and pyruvate carboxylase enhance glutathione synthesis and restrict oxidative stress in pancreatic islets. (2021). https://pubmed.ncbi.nlm.nih.gov/34818536/ DOI: 10.1016/j.celrep.2021.110037
tissue_or_cell_type
Primary human pancreatic islets
trigger_kind
machinery_impairment Imported condition classification; unverified.
Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17) · lines 871–882
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary human-islet tracer metabolomics and PC knockdown under inflammatory/nitrosative stress · source_derived_draft · unverified_draft
### b7-pc-islet-gsh Genetic depletion of PC in human islets reduced glutathione and the GSH/GSSG ratio under nitrosative stress. Condition category: machinery_impairment nutrient_topic: Biotin research collection; topical membership is not evidence of a direct dietary effect. plain_language: PC connects carbon metabolism to the cell’s ability to maintain glutathione. organism: Homo sapiens tissue_or_cell_type: Primary human pancreatic islets experimental_model: Primary human-islet tracer metabolomics and PC knockdown under inflammatory/nitrosative stress limitations: Genetic perturbation of PC in isolated islets is not dietary biotin depletion or evidence that biotin supplements raise glutathione in replete people. exposure: Glucose tracer, PC knockdown and nitric-oxide donor exposure evidence_span: {"source_cache": "artifacts/biotin-research/34818536.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "48bcb3951c9b630862fdda839e0a54b80abe9e2cf2e79d0bfb7547e2af317523", "start_char": 35800, "end_char": 36138, "text_sha256": "b1dd7e5022ba64d19114d853d2f75c43e061cdca76e1938e95c19379e96c3933"} [b7-p34818536] Glucose metabolism and pyruvate carboxylase enhance glutathione synthesis and restrict oxidative stress in pancreatic islets. (2021). https://pubmed.ncbi.nlm.nih.gov/34818536/ DOI: 10.1016/j.celrep.2021.110037
Complete structured claim and evidence
Pdss2-mutant kidneys had glutathione depletion, whereas the less CoQ-depleted brain lacked these abnormalities.
Mouse Pdss2 → GSH source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/coq10-research/27856618.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8b98767d3bed9661c05c7b82b55817b6d9912abd8bfc9dd9d59ca9763025485", "start_char": 0, "end_char": 1261, "text_sha256": "a8b98767d3bed9661c05c7b82b55817b6d9912abd8bfc9dd9d59ca9763025485"}
experimental_model
Patient fibroblasts, biosynthesis inhibition and mouse genetics
exposure
Genetic or pharmacological CoQ depletion and in-vitro repletion
limitations
Tissue-specific disease models; mouse residual percentages are not diagnostic human thresholds.
nutrient_topic
Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. · Coenzyme Q10 / CoQ10 redox system
organism
Human fibroblasts/HeLa cells and Pdss2 mutant mice
plain_language
The CoQ defect connected to another antioxidant pool in this kidney model.
primary_references
[coq10-p27856618] Coenzyme Q deficiency causes impairment of the sulfide oxidation pathway. (2017). https://pubmed.ncbi.nlm.nih.gov/27856618/ DOI: 10.15252/emmm.201606356
tissue_or_cell_type
Sulfide oxidation and tissue CoQ
trigger_kind
machinery_impairment Imported condition classification; unverified.
Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17) · lines 580–591
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient fibroblasts, biosynthesis inhibition and mouse genetics · source_derived_draft · unverified_draft
### coq10-kidney-glutathione Pdss2-mutant kidneys had glutathione depletion, whereas the less CoQ-depleted brain lacked these abnormalities. Condition category: machinery_impairment nutrient_topic: Coenzyme Q10 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The CoQ defect connected to another antioxidant pool in this kidney model. organism: Human fibroblasts/HeLa cells and Pdss2 mutant mice tissue_or_cell_type: Sulfide oxidation and tissue CoQ experimental_model: Patient fibroblasts, biosynthesis inhibition and mouse genetics limitations: Tissue-specific disease models; mouse residual percentages are not diagnostic human thresholds. exposure: Genetic or pharmacological CoQ depletion and in-vitro repletion evidence_span: {"source_cache": "artifacts/coq10-research/27856618.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a8b98767d3bed9661c05c7b82b55817b6d9912abd8bfc9dd9d59ca9763025485", "start_char": 0, "end_char": 1261, "text_sha256": "a8b98767d3bed9661c05c7b82b55817b6d9912abd8bfc9dd9d59ca9763025485"} [coq10-p27856618] Coenzyme Q deficiency causes impairment of the sulfide oxidation pathway. (2017). https://pubmed.ncbi.nlm.nih.gov/27856618/ DOI: 10.15252/emmm.201606356
Complete structured claim and evidence
Glutathione reduced fully oxidized apo-COX17 back to the two-disulfide state in the protein-transfer system.
GSH → Human apo-COX17 with three disulfides source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/copper-research/18458339.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1e2740a864c2c21568eae7933027e4c9bb16b985478ebbf946d4d2067ba777f8", "start_char": 0, "end_char": 1482, "text_sha256": "1e2740a864c2c21568eae7933027e4c9bb16b985478ebbf946d4d2067ba777f8"}
experimental_model
Purified-protein metal and electron transfer experiments
exposure
Defined COX17 and SCO redox states; glutathione reduction
limitations
Biochemical transfer mechanism; the same coupled reaction was not observed with SCO2. These results are not proof that glutathione supplementation repairs COX assembly.
nutrient_topic
Copper research collection; topical membership is not evidence of a direct dietary effect. · Copper
organism
Human proteins
plain_language
Glutathione helps reset a mitochondrial copper courier.
primary_references
[copper-p18458339] Mitochondrial copper(I) transfer from Cox17 to Sco1 is coupled to electron transfer. (2008). https://pubmed.ncbi.nlm.nih.gov/18458339/ DOI: 10.1073/pnas.0800019105
tissue_or_cell_type
Mitochondrial intermembrane-space protein system
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17) · lines 624–635
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified-protein metal and electron transfer experiments · source_derived_draft · unverified_draft
### copper-glutathione-cox17-recycling Glutathione reduced fully oxidized apo-COX17 back to the two-disulfide state in the protein-transfer system. Condition category: normal nutrient_topic: Copper research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione helps reset a mitochondrial copper courier. organism: Human proteins tissue_or_cell_type: Mitochondrial intermembrane-space protein system experimental_model: Purified-protein metal and electron transfer experiments limitations: Biochemical transfer mechanism; the same coupled reaction was not observed with SCO2. These results are not proof that glutathione supplementation repairs COX assembly. exposure: Defined COX17 and SCO redox states; glutathione reduction evidence_span: {"source_cache": "artifacts/copper-research/18458339.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "1e2740a864c2c21568eae7933027e4c9bb16b985478ebbf946d4d2067ba777f8", "start_char": 0, "end_char": 1482, "text_sha256": "1e2740a864c2c21568eae7933027e4c9bb16b985478ebbf946d4d2067ba777f8"} [copper-p18458339] Mitochondrial copper(I) transfer from Cox17 to Sco1 is coupled to electron transfer. (2008). https://pubmed.ncbi.nlm.nih.gov/18458339/ DOI: 10.1073/pnas.0800019105
Complete structured claim and evidence
Glutathione protected recombinant MTF1 from cadmium-mediated inactivation, allowing zinc-dependent DNA-binding activity in the assay.
GSH → MTF1 binding to metal-responsive DNA elements source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Human metal-regulatory transcription factor 1 / MTF1 (human_protein); Mouse metal-regulatory transcription factor 1 / Mtf1 (mouse_protein); Zinc(II) ion (activating_ion)
evidence_span
{"source_cache": "artifacts/zinc-signaling-sources/9507026-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "ecd19e16b15909d46328c2c5dcd9f9536422db7bb12b9dfd9d91763fafe164bd"}
experimental_model
Human and mouse cell extracts and recombinant MTF1
exposure
Zinc versus other tested transition metals; DNA-binding assays. Glutathione was 1 mM in the recombinant-protein cadmium challenge; this is an in-vitro assay concentration.
limitations
In-vitro metal specificity does not mean all cellular metal responses are mediated by direct MTF1 binding.
nutrient_topic
Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc
organism
Homo sapiens; Mus musculus
plain_language
Glutathione helped preserve the zinc-dependent sensor under this chemical stress.
primary_references
[zn-sig-9507026] The DNA binding activity of metal response element-binding transcription factor-1 is activated in vivo and in vitro by zinc, but not by other transition metals. (1998). https://pubmed.ncbi.nlm.nih.gov/9507026/ DOI: 10.1074/jbc.273.12.7127
tissue_or_cell_type
Cell extracts and recombinant protein
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 887–899
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human and mouse cell extracts and recombinant MTF1 · source_derived_draft · unverified_draft
### zn-sig-gsh-mtf1-protection Glutathione protected recombinant MTF1 from cadmium-mediated inactivation, allowing zinc-dependent DNA-binding activity in the assay. Condition category: normal nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione helped preserve the zinc-dependent sensor under this chemical stress. organism: Homo sapiens; Mus musculus tissue_or_cell_type: Cell extracts and recombinant protein experimental_model: Human and mouse cell extracts and recombinant MTF1 limitations: In-vitro metal specificity does not mean all cellular metal responses are mediated by direct MTF1 binding. exposure: Zinc versus other tested transition metals; DNA-binding assays. Glutathione was 1 mM in the recombinant-protein cadmium challenge; this is an in-vitro assay concentration. cross_nutrient: Human metal-regulatory transcription factor 1 / MTF1 (human_protein); Mouse metal-regulatory transcription factor 1 / Mtf1 (mouse_protein); Zinc(II) ion (activating_ion) evidence_span: {"source_cache": "artifacts/zinc-signaling-sources/9507026-abstract.txt", "locator": "Primary indexed abstract", "file_sha256": "ecd19e16b15909d46328c2c5dcd9f9536422db7bb12b9dfd9d91763fafe164bd"} [zn-sig-9507026] The DNA binding activity of metal response element-binding transcription factor-1 is activated in vivo and in vitro by zinc, but not by other transition metals. (1998). https://pubmed.ncbi.nlm.nih.gov/9507026/ DOI: 10.1074/jbc.273.12.7127
Complete structured claim and evidence
Purified human glutathione reductase reduced free lipoic acid to DHLA in vitro.
Glutathione reductase / GSR → Lipoic acid source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/7632170.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ebbc851e5279e646bc7c892645c931a3fd2993830c3f4405379839cbbd6e707", "start_char": 0, "end_char": 1863, "text_sha256": "2ebbc851e5279e646bc7c892645c931a3fd2993830c3f4405379839cbbd6e707"}
experimental_model
Human erythrocytes, one G6PD-deficient donor and purified-enzyme assays
exposure
Lipoic acid with glucose/2-deoxyglucose and G6PD inhibition
limitations
The deficient-donor finding is small and mechanistic; it is not a clinical safety or efficacy trial in G6PD deficiency.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human
plain_language
An enzyme associated with glutathione recycling can also reduce free lipoic acid.
primary_references
[ala-p7632170] Reduction and transport of lipoic acid by human erythrocytes. (1995). https://pubmed.ncbi.nlm.nih.gov/7632170/ DOI: 10.1016/0006-2952(95)00084-d
tissue_or_cell_type
Erythrocytes and glutathione reductase
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 741–752
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human erythrocytes, one G6PD-deficient donor and purified-enzyme assays · source_derived_draft · unverified_draft
### ala-gsr-free-lipoate Purified human glutathione reductase reduced free lipoic acid to DHLA in vitro. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: An enzyme associated with glutathione recycling can also reduce free lipoic acid. organism: Human tissue_or_cell_type: Erythrocytes and glutathione reductase experimental_model: Human erythrocytes, one G6PD-deficient donor and purified-enzyme assays limitations: The deficient-donor finding is small and mechanistic; it is not a clinical safety or efficacy trial in G6PD deficiency. exposure: Lipoic acid with glucose/2-deoxyglucose and G6PD inhibition evidence_span: {"source_cache": "artifacts/ala-research/7632170.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "2ebbc851e5279e646bc7c892645c931a3fd2993830c3f4405379839cbbd6e707", "start_char": 0, "end_char": 1863, "text_sha256": "2ebbc851e5279e646bc7c892645c931a3fd2993830c3f4405379839cbbd6e707"} [ala-p7632170] Reduction and transport of lipoic acid by human erythrocytes. (1995). https://pubmed.ncbi.nlm.nih.gov/7632170/ DOI: 10.1016/0006-2952(95)00084-d
Complete structured claim and evidence
Reduced glutathione concentrations did not change significantly in thalamus or cortex on days 13 or 14.
Thiamine (vitamin B1) → GSH source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_location
Abstract; Figure 1B
evidence_span
No significant changes in GSH concentration
experimental_model
Male Sprague-Dawley rats, eight weeks old; thiamine-deficient chow plus daily pyrithiamine 0.25 mg/kg intraperitoneally; pair-fed thiamine-injected controls; days 13 and 14 brain assays.
exposure
Thiamine-deficient chow plus pyrithiamine, day 14 with seizures and absent righting reflex
limitations
Total regional concentration does not measure glutathione turnover or subcellular redox state; no direct NADPH result is inferred.
nutrient_topic
Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
organism
Rattus norvegicus
plain_language
Higher oxidant signals did not require a detectable fall in the measured glutathione pool.
primary_references
[langlais-1997-brain-oxidants] Increased cerebral free radical production during thiamine deficiency (1997). https://pubmed.ncbi.nlm.nih.gov/9203158/ DOI: 10.1007/BF02674735
tissue_or_cell_type
Thalamus and cortex
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1169–1181
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Male Sprague-Dawley rats, eight weeks old; thiamine-deficient chow plus daily pyrithiamine 0.25 mg/kg intraperitoneally; pair-fed thiamine-injected controls; days 13 and 14 brain assays. · source_derived_draft · unverified_draft
### thiamine-def-glutathione-preserved-oxidant-context Reduced glutathione concentrations did not change significantly in thalamus or cortex on days 13 or 14. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Higher oxidant signals did not require a detectable fall in the measured glutathione pool. organism: Rattus norvegicus tissue_or_cell_type: Thalamus and cortex experimental_model: Male Sprague-Dawley rats, eight weeks old; thiamine-deficient chow plus daily pyrithiamine 0.25 mg/kg intraperitoneally; pair-fed thiamine-injected controls; days 13 and 14 brain assays. limitations: Total regional concentration does not measure glutathione turnover or subcellular redox state; no direct NADPH result is inferred. evidence_location: Abstract; Figure 1B evidence_span: No significant changes in GSH concentration exposure: Thiamine-deficient chow plus pyrithiamine, day 14 with seizures and absent righting reflex [langlais-1997-brain-oxidants] Increased cerebral free radical production during thiamine deficiency (1997). https://pubmed.ncbi.nlm.nih.gov/9203158/ DOI: 10.1007/BF02674735
Complete structured claim and evidence
SUOX-deficient cells accumulated persulfidated glutathione and cysteine.
Human sulfite oxidase / SUOX → Glutathione persulfide / GSSH source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
{"source_cache": "artifacts/molybdenum-research/33271457.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "619710a31160db0927e01193e458277773ebe5e5423629e7dab58888ab6bc617", "start_char": 0, "end_char": 1479, "text_sha256": "619710a31160db0927e01193e458277773ebe5e5423629e7dab58888ab6bc617"}
experimental_model
CRISPR SUOX/GOT1/GOT2 perturbations and sulfur-metabolite assays
exposure
Cysteine-sulfinate and H2S pathway experiments
limitations
Cell-specific contributions; a higher concentration is not a direct measurement of pathway flux.
nutrient_topic
Molybdenum research collection; topical membership is not evidence of a direct dietary effect. · Molybdenum
organism
Homo sapiens
plain_language
Glutathione and cysteine sulfur chemistry also changed.
primary_references
[mo-p33271457] The role of glutamate oxaloacetate transaminases in sulfite biosynthesis and H<sub>2</sub>S metabolism. (2021). https://pubmed.ncbi.nlm.nih.gov/33271457/ DOI: 10.1016/j.redox.2020.101800
tissue_or_cell_type
HEK293T cells
trigger_kind
machinery_impairment Imported condition classification; unverified.
Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 716–727
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CRISPR SUOX/GOT1/GOT2 perturbations and sulfur-metabolite assays · source_derived_draft · unverified_draft
### mo-suox-persulfides SUOX-deficient cells accumulated persulfidated glutathione and cysteine. Condition category: machinery_impairment nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione and cysteine sulfur chemistry also changed. organism: Homo sapiens tissue_or_cell_type: HEK293T cells experimental_model: CRISPR SUOX/GOT1/GOT2 perturbations and sulfur-metabolite assays limitations: Cell-specific contributions; a higher concentration is not a direct measurement of pathway flux. exposure: Cysteine-sulfinate and H2S pathway experiments evidence_span: {"source_cache": "artifacts/molybdenum-research/33271457.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "619710a31160db0927e01193e458277773ebe5e5423629e7dab58888ab6bc617", "start_char": 0, "end_char": 1479, "text_sha256": "619710a31160db0927e01193e458277773ebe5e5423629e7dab58888ab6bc617"} [mo-p33271457] The role of glutamate oxaloacetate transaminases in sulfite biosynthesis and H<sub>2</sub>S metabolism. (2021). https://pubmed.ncbi.nlm.nih.gov/33271457/ DOI: 10.1016/j.redox.2020.101800
Complete structured claim and evidence
The abstract reports DLAT binding to SLC25A39 in colorectal cancer models.
Dihydrolipoyl acetyltransferase / DLAT → Human mitochondrial glutathione carrier SLC25A39 source_derived_draftungraded
Experimental context and source evidence
access_level
abstract_only
compartment
Mitochondrial GSH versus intracellular GSH distinguished by authors
dose
Unknown: full methods unavailable
duration
Unknown: full methods unavailable
endpoint
slc25a39
evidence_location
Primary indexed abstract; experiment-specific methods unavailable
experimental_model
Protein interaction/stability, knockdown and compound experiments reported in abstract
exposure
dlat
limitations
ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference.
nutrient_topic
Topical cross-reference only; no inheritance of another actor's effects. · GSH
organism
Human colorectal cancer models; individual experiments require full-text confirmation
plain_language
The abstract reports DLAT binding to SLC25A39 in colorectal cancer models.
primary_locator
[{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}]
primary_references
https://doi.org/10.1016/j.freeradbiomed.2026.04.133
tissue_or_cell_type
Colorectal cancer models; claim-specific cell line not established from abstract
DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 716–730
AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Protein interaction/stability, knockdown and compound experiments reported in abstract · source_derived_draft · unverified_draft
The abstract reports DLAT binding to SLC25A39 in colorectal cancer models. organism: Human colorectal cancer models; individual experiments require full-text confirmation tissue_or_cell_type: Colorectal cancer models; claim-specific cell line not established from abstract experimental_model: Protein interaction/stability, knockdown and compound experiments reported in abstract compartment: Mitochondrial GSH versus intracellular GSH distinguished by authors dose: Unknown: full methods unavailable duration: Unknown: full methods unavailable primary_references: https://doi.org/10.1016/j.freeradbiomed.2026.04.133 access_level: abstract_only evidence_location: Primary indexed abstract; experiment-specific methods unavailable endpoint: slc25a39 exposure: dlat limitations: ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference. primary_locator: [{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}] plain_language: The abstract reports DLAT binding to SLC25A39 in colorectal cancer models.
Complete structured claim and evidence
DLAT reportedly stabilized SLC25A39 independently of intracellular glutathione levels.
Dihydrolipoyl acetyltransferase / DLAT → SLC25A39 protein stability source_derived_draftungraded
Experimental context and source evidence
access_level
abstract_only
compartment
Mitochondrial GSH versus intracellular GSH distinguished by authors
dose
Unknown: full methods unavailable
duration
Unknown: full methods unavailable
endpoint
slc25a39-protein-stability
evidence_location
Primary indexed abstract; experiment-specific methods unavailable
experimental_model
Protein interaction/stability, knockdown and compound experiments reported in abstract
exposure
dlat
limitations
ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference.
nutrient_topic
Topical cross-reference only; no inheritance of another actor's effects. · GSH
organism
Human colorectal cancer models; individual experiments require full-text confirmation
plain_language
DLAT reportedly stabilized SLC25A39 independently of intracellular glutathione levels.
primary_locator
[{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}]
primary_references
https://doi.org/10.1016/j.freeradbiomed.2026.04.133
tissue_or_cell_type
Colorectal cancer models; claim-specific cell line not established from abstract
DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 733–747
AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Protein interaction/stability, knockdown and compound experiments reported in abstract · source_derived_draft · unverified_draft
DLAT reportedly stabilized SLC25A39 independently of intracellular glutathione levels. organism: Human colorectal cancer models; individual experiments require full-text confirmation tissue_or_cell_type: Colorectal cancer models; claim-specific cell line not established from abstract experimental_model: Protein interaction/stability, knockdown and compound experiments reported in abstract compartment: Mitochondrial GSH versus intracellular GSH distinguished by authors dose: Unknown: full methods unavailable duration: Unknown: full methods unavailable primary_references: https://doi.org/10.1016/j.freeradbiomed.2026.04.133 access_level: abstract_only evidence_location: Primary indexed abstract; experiment-specific methods unavailable endpoint: slc25a39-protein-stability exposure: dlat limitations: ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference. primary_locator: [{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}] plain_language: DLAT reportedly stabilized SLC25A39 independently of intracellular glutathione levels.
Complete structured claim and evidence
The authors connect DLAT-associated transporter stabilization with maintained mitochondrial glutathione import.
Dihydrolipoyl acetyltransferase / DLAT → Mammalian mitochondrial glutathione import source_derived_draftungraded
Experimental context and source evidence
access_level
abstract_only
compartment
Mitochondrial GSH versus intracellular GSH distinguished by authors
dose
Unknown: full methods unavailable
duration
Unknown: full methods unavailable
endpoint
mitochondrial-gsh-import
evidence_location
Primary indexed abstract; experiment-specific methods unavailable
experimental_model
Protein interaction/stability, knockdown and compound experiments reported in abstract
exposure
dlat
limitations
ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference. Mechanistic interpretation reported in abstract; mediation/rescue controls cannot be assessed without full text.
nutrient_topic
Topical cross-reference only; no inheritance of another actor's effects. · GSH
organism
Human colorectal cancer models; individual experiments require full-text confirmation
plain_language
The authors connect DLAT-associated transporter stabilization with maintained mitochondrial glutathione import.
primary_locator
[{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}]
primary_references
https://doi.org/10.1016/j.freeradbiomed.2026.04.133
tissue_or_cell_type
Colorectal cancer models; claim-specific cell line not established from abstract
DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 750–764
AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Protein interaction/stability, knockdown and compound experiments reported in abstract · source_derived_draft · unverified_draft
The authors connect DLAT-associated transporter stabilization with maintained mitochondrial glutathione import. organism: Human colorectal cancer models; individual experiments require full-text confirmation tissue_or_cell_type: Colorectal cancer models; claim-specific cell line not established from abstract experimental_model: Protein interaction/stability, knockdown and compound experiments reported in abstract compartment: Mitochondrial GSH versus intracellular GSH distinguished by authors dose: Unknown: full methods unavailable duration: Unknown: full methods unavailable primary_references: https://doi.org/10.1016/j.freeradbiomed.2026.04.133 access_level: abstract_only evidence_location: Primary indexed abstract; experiment-specific methods unavailable endpoint: mitochondrial-gsh-import exposure: dlat limitations: ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference. Mechanistic interpretation reported in abstract; mediation/rescue controls cannot be assessed without full text. primary_locator: [{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}] plain_language: The authors connect DLAT-associated transporter stabilization with maintained mitochondrial glutathione import.
Complete structured claim and evidence
DLAT knockdown reportedly disrupted mitochondrial glutathione transport.
DLAT knockdown in human colorectal cancer models → Mammalian mitochondrial glutathione import source_derived_draftungraded
Experimental context and source evidence
access_level
abstract_only
compartment
Mitochondrial GSH versus intracellular GSH distinguished by authors
dose
Unknown: full methods unavailable
duration
Unknown: full methods unavailable
endpoint
mitochondrial-gsh-import
evidence_location
Primary indexed abstract; experiment-specific methods unavailable
experimental_model
Protein interaction/stability, knockdown and compound experiments reported in abstract
exposure
human-crc-dlat-knockdown
limitations
ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference.
nutrient_topic
Topical cross-reference only; no inheritance of another actor's effects. · GSH
organism
Human colorectal cancer models; individual experiments require full-text confirmation
plain_language
DLAT knockdown reportedly disrupted mitochondrial glutathione transport.
primary_locator
[{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}]
primary_references
https://doi.org/10.1016/j.freeradbiomed.2026.04.133
tissue_or_cell_type
Colorectal cancer models; claim-specific cell line not established from abstract
DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 767–781
AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Protein interaction/stability, knockdown and compound experiments reported in abstract · source_derived_draft · unverified_draft
DLAT knockdown reportedly disrupted mitochondrial glutathione transport. organism: Human colorectal cancer models; individual experiments require full-text confirmation tissue_or_cell_type: Colorectal cancer models; claim-specific cell line not established from abstract experimental_model: Protein interaction/stability, knockdown and compound experiments reported in abstract compartment: Mitochondrial GSH versus intracellular GSH distinguished by authors dose: Unknown: full methods unavailable duration: Unknown: full methods unavailable primary_references: https://doi.org/10.1016/j.freeradbiomed.2026.04.133 access_level: abstract_only evidence_location: Primary indexed abstract; experiment-specific methods unavailable endpoint: mitochondrial-gsh-import exposure: human-crc-dlat-knockdown limitations: ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference. primary_locator: [{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}] plain_language: DLAT knockdown reportedly disrupted mitochondrial glutathione transport.
Complete structured claim and evidence
DLAT knockdown reportedly increased lipid peroxidation.
DLAT knockdown in human colorectal cancer models → Lipid peroxidation source_derived_draftungraded
Experimental context and source evidence
access_level
abstract_only
compartment
Mitochondrial GSH versus intracellular GSH distinguished by authors
dose
Unknown: full methods unavailable
duration
Unknown: full methods unavailable
endpoint
lipid-peroxidation
evidence_location
Primary indexed abstract; experiment-specific methods unavailable
experimental_model
Protein interaction/stability, knockdown and compound experiments reported in abstract
exposure
human-crc-dlat-knockdown
limitations
ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference.
nutrient_topic
Topical cross-reference only; no inheritance of another actor's effects. · GSH
organism
Human colorectal cancer models; individual experiments require full-text confirmation
plain_language
DLAT knockdown reportedly increased lipid peroxidation.
primary_locator
[{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}]
primary_references
https://doi.org/10.1016/j.freeradbiomed.2026.04.133
tissue_or_cell_type
Colorectal cancer models; claim-specific cell line not established from abstract
DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 784–798
AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Protein interaction/stability, knockdown and compound experiments reported in abstract · source_derived_draft · unverified_draft
DLAT knockdown reportedly increased lipid peroxidation. organism: Human colorectal cancer models; individual experiments require full-text confirmation tissue_or_cell_type: Colorectal cancer models; claim-specific cell line not established from abstract experimental_model: Protein interaction/stability, knockdown and compound experiments reported in abstract compartment: Mitochondrial GSH versus intracellular GSH distinguished by authors dose: Unknown: full methods unavailable duration: Unknown: full methods unavailable primary_references: https://doi.org/10.1016/j.freeradbiomed.2026.04.133 access_level: abstract_only evidence_location: Primary indexed abstract; experiment-specific methods unavailable endpoint: lipid-peroxidation exposure: human-crc-dlat-knockdown limitations: ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference. primary_locator: [{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}] plain_language: DLAT knockdown reportedly increased lipid peroxidation.
Complete structured claim and evidence
DLAT knockdown reportedly increased ferroptosis susceptibility.
DLAT knockdown in human colorectal cancer models → Ferroptosis source_derived_draftungraded
Experimental context and source evidence
access_level
abstract_only
compartment
Mitochondrial GSH versus intracellular GSH distinguished by authors
dose
Unknown: full methods unavailable
duration
Unknown: full methods unavailable
endpoint
ferroptosis
evidence_location
Primary indexed abstract; experiment-specific methods unavailable
experimental_model
Protein interaction/stability, knockdown and compound experiments reported in abstract
exposure
human-crc-dlat-knockdown
limitations
ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference. The abstract does not identify each inducing exposure or rescue control.
nutrient_topic
Topical cross-reference only; no inheritance of another actor's effects. · GSH
organism
Human colorectal cancer models; individual experiments require full-text confirmation
plain_language
DLAT knockdown reportedly increased ferroptosis susceptibility.
primary_locator
[{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}]
primary_references
https://doi.org/10.1016/j.freeradbiomed.2026.04.133
tissue_or_cell_type
Colorectal cancer models; claim-specific cell line not established from abstract
DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 801–815
AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Protein interaction/stability, knockdown and compound experiments reported in abstract · source_derived_draft · unverified_draft
DLAT knockdown reportedly increased ferroptosis susceptibility. organism: Human colorectal cancer models; individual experiments require full-text confirmation tissue_or_cell_type: Colorectal cancer models; claim-specific cell line not established from abstract experimental_model: Protein interaction/stability, knockdown and compound experiments reported in abstract compartment: Mitochondrial GSH versus intracellular GSH distinguished by authors dose: Unknown: full methods unavailable duration: Unknown: full methods unavailable primary_references: https://doi.org/10.1016/j.freeradbiomed.2026.04.133 access_level: abstract_only evidence_location: Primary indexed abstract; experiment-specific methods unavailable endpoint: ferroptosis exposure: human-crc-dlat-knockdown limitations: ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference. The abstract does not identify each inducing exposure or rescue control. primary_locator: [{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}] plain_language: DLAT knockdown reportedly increased ferroptosis susceptibility.
Complete structured claim and evidence
SLC25A39 knockdown reportedly disrupted mitochondrial glutathione transport.
SLC25A39 knockdown in human colorectal cancer models → Mammalian mitochondrial glutathione import source_derived_draftungraded
Experimental context and source evidence
access_level
abstract_only
compartment
Mitochondrial GSH versus intracellular GSH distinguished by authors
dose
Unknown: full methods unavailable
duration
Unknown: full methods unavailable
endpoint
mitochondrial-gsh-import
evidence_location
Primary indexed abstract; experiment-specific methods unavailable
experimental_model
Protein interaction/stability, knockdown and compound experiments reported in abstract
exposure
human-crc-slc25a39-knockdown
limitations
ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference.
nutrient_topic
Topical cross-reference only; no inheritance of another actor's effects. · GSH
organism
Human colorectal cancer models; individual experiments require full-text confirmation
plain_language
SLC25A39 knockdown reportedly disrupted mitochondrial glutathione transport.
primary_locator
[{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}]
primary_references
https://doi.org/10.1016/j.freeradbiomed.2026.04.133
tissue_or_cell_type
Colorectal cancer models; claim-specific cell line not established from abstract
DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 818–832
AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Protein interaction/stability, knockdown and compound experiments reported in abstract · source_derived_draft · unverified_draft
SLC25A39 knockdown reportedly disrupted mitochondrial glutathione transport. organism: Human colorectal cancer models; individual experiments require full-text confirmation tissue_or_cell_type: Colorectal cancer models; claim-specific cell line not established from abstract experimental_model: Protein interaction/stability, knockdown and compound experiments reported in abstract compartment: Mitochondrial GSH versus intracellular GSH distinguished by authors dose: Unknown: full methods unavailable duration: Unknown: full methods unavailable primary_references: https://doi.org/10.1016/j.freeradbiomed.2026.04.133 access_level: abstract_only evidence_location: Primary indexed abstract; experiment-specific methods unavailable endpoint: mitochondrial-gsh-import exposure: human-crc-slc25a39-knockdown limitations: ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference. primary_locator: [{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}] plain_language: SLC25A39 knockdown reportedly disrupted mitochondrial glutathione transport.
Complete structured claim and evidence
SLC25A39 knockdown reportedly increased lipid peroxidation.
SLC25A39 knockdown in human colorectal cancer models → Lipid peroxidation source_derived_draftungraded
Experimental context and source evidence
access_level
abstract_only
compartment
Mitochondrial GSH versus intracellular GSH distinguished by authors
dose
Unknown: full methods unavailable
duration
Unknown: full methods unavailable
endpoint
lipid-peroxidation
evidence_location
Primary indexed abstract; experiment-specific methods unavailable
experimental_model
Protein interaction/stability, knockdown and compound experiments reported in abstract
exposure
human-crc-slc25a39-knockdown
limitations
ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference.
nutrient_topic
Topical cross-reference only; no inheritance of another actor's effects. · GSH
organism
Human colorectal cancer models; individual experiments require full-text confirmation
plain_language
SLC25A39 knockdown reportedly increased lipid peroxidation.
primary_locator
[{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}]
primary_references
https://doi.org/10.1016/j.freeradbiomed.2026.04.133
tissue_or_cell_type
Colorectal cancer models; claim-specific cell line not established from abstract
DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 835–849
AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Protein interaction/stability, knockdown and compound experiments reported in abstract · source_derived_draft · unverified_draft
SLC25A39 knockdown reportedly increased lipid peroxidation. organism: Human colorectal cancer models; individual experiments require full-text confirmation tissue_or_cell_type: Colorectal cancer models; claim-specific cell line not established from abstract experimental_model: Protein interaction/stability, knockdown and compound experiments reported in abstract compartment: Mitochondrial GSH versus intracellular GSH distinguished by authors dose: Unknown: full methods unavailable duration: Unknown: full methods unavailable primary_references: https://doi.org/10.1016/j.freeradbiomed.2026.04.133 access_level: abstract_only evidence_location: Primary indexed abstract; experiment-specific methods unavailable endpoint: lipid-peroxidation exposure: human-crc-slc25a39-knockdown limitations: ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference. primary_locator: [{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}] plain_language: SLC25A39 knockdown reportedly increased lipid peroxidation.
Complete structured claim and evidence
SLC25A39 knockdown reportedly increased ferroptosis susceptibility.
SLC25A39 knockdown in human colorectal cancer models → Ferroptosis source_derived_draftungraded
Experimental context and source evidence
access_level
abstract_only
compartment
Mitochondrial GSH versus intracellular GSH distinguished by authors
dose
Unknown: full methods unavailable
duration
Unknown: full methods unavailable
endpoint
ferroptosis
evidence_location
Primary indexed abstract; experiment-specific methods unavailable
experimental_model
Protein interaction/stability, knockdown and compound experiments reported in abstract
exposure
human-crc-slc25a39-knockdown
limitations
ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference. The abstract does not identify each inducing exposure or rescue control.
nutrient_topic
Topical cross-reference only; no inheritance of another actor's effects. · GSH
organism
Human colorectal cancer models; individual experiments require full-text confirmation
plain_language
SLC25A39 knockdown reportedly increased ferroptosis susceptibility.
primary_locator
[{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}]
primary_references
https://doi.org/10.1016/j.freeradbiomed.2026.04.133
tissue_or_cell_type
Colorectal cancer models; claim-specific cell line not established from abstract
DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 852–866
AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Protein interaction/stability, knockdown and compound experiments reported in abstract · source_derived_draft · unverified_draft
SLC25A39 knockdown reportedly increased ferroptosis susceptibility. organism: Human colorectal cancer models; individual experiments require full-text confirmation tissue_or_cell_type: Colorectal cancer models; claim-specific cell line not established from abstract experimental_model: Protein interaction/stability, knockdown and compound experiments reported in abstract compartment: Mitochondrial GSH versus intracellular GSH distinguished by authors dose: Unknown: full methods unavailable duration: Unknown: full methods unavailable primary_references: https://doi.org/10.1016/j.freeradbiomed.2026.04.133 access_level: abstract_only evidence_location: Primary indexed abstract; experiment-specific methods unavailable endpoint: ferroptosis exposure: human-crc-slc25a39-knockdown limitations: ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference. The abstract does not identify each inducing exposure or rescue control. primary_locator: [{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}] plain_language: SLC25A39 knockdown reportedly increased ferroptosis susceptibility.
Complete structured claim and evidence
GL-V9 reportedly bound DLAT.
GL-V9 → Dihydrolipoyl acetyltransferase / DLAT source_derived_draftungraded
Experimental context and source evidence
access_level
abstract_only
compartment
Mitochondrial GSH versus intracellular GSH distinguished by authors
dose
Unknown: full methods unavailable
duration
Unknown: full methods unavailable
endpoint
dlat
evidence_location
Primary indexed abstract; experiment-specific methods unavailable
experimental_model
Protein interaction/stability, knockdown and compound experiments reported in abstract
exposure
gl-v9
limitations
ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference.
nutrient_topic
Topical cross-reference only; no inheritance of another actor's effects. · GSH
organism
Human colorectal cancer models; individual experiments require full-text confirmation
plain_language
GL-V9 reportedly bound DLAT.
primary_locator
[{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}]
primary_references
https://doi.org/10.1016/j.freeradbiomed.2026.04.133
tissue_or_cell_type
Colorectal cancer models; claim-specific cell line not established from abstract
DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 869–883
AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Protein interaction/stability, knockdown and compound experiments reported in abstract · source_derived_draft · unverified_draft
GL-V9 reportedly bound DLAT. organism: Human colorectal cancer models; individual experiments require full-text confirmation tissue_or_cell_type: Colorectal cancer models; claim-specific cell line not established from abstract experimental_model: Protein interaction/stability, knockdown and compound experiments reported in abstract compartment: Mitochondrial GSH versus intracellular GSH distinguished by authors dose: Unknown: full methods unavailable duration: Unknown: full methods unavailable primary_references: https://doi.org/10.1016/j.freeradbiomed.2026.04.133 access_level: abstract_only evidence_location: Primary indexed abstract; experiment-specific methods unavailable endpoint: dlat exposure: gl-v9 limitations: ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference. primary_locator: [{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}] plain_language: GL-V9 reportedly bound DLAT.
Complete structured claim and evidence
GL-V9 reportedly promoted ubiquitin-proteasome degradation of DLAT.
GL-V9 → DLAT ubiquitin-proteasome degradation source_derived_draftungraded
Experimental context and source evidence
access_level
abstract_only
compartment
Mitochondrial GSH versus intracellular GSH distinguished by authors
dose
Unknown: full methods unavailable
duration
Unknown: full methods unavailable
endpoint
dlat-ubiquitin-proteasome-degradation
evidence_location
Primary indexed abstract; experiment-specific methods unavailable
experimental_model
Protein interaction/stability, knockdown and compound experiments reported in abstract
exposure
gl-v9
limitations
ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference.
nutrient_topic
Topical cross-reference only; no inheritance of another actor's effects. · GSH
organism
Human colorectal cancer models; individual experiments require full-text confirmation
plain_language
GL-V9 reportedly promoted ubiquitin-proteasome degradation of DLAT.
primary_locator
[{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}]
primary_references
https://doi.org/10.1016/j.freeradbiomed.2026.04.133
tissue_or_cell_type
Colorectal cancer models; claim-specific cell line not established from abstract
DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 886–900
AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Protein interaction/stability, knockdown and compound experiments reported in abstract · source_derived_draft · unverified_draft
GL-V9 reportedly promoted ubiquitin-proteasome degradation of DLAT. organism: Human colorectal cancer models; individual experiments require full-text confirmation tissue_or_cell_type: Colorectal cancer models; claim-specific cell line not established from abstract experimental_model: Protein interaction/stability, knockdown and compound experiments reported in abstract compartment: Mitochondrial GSH versus intracellular GSH distinguished by authors dose: Unknown: full methods unavailable duration: Unknown: full methods unavailable primary_references: https://doi.org/10.1016/j.freeradbiomed.2026.04.133 access_level: abstract_only evidence_location: Primary indexed abstract; experiment-specific methods unavailable endpoint: dlat-ubiquitin-proteasome-degradation exposure: gl-v9 limitations: ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference. primary_locator: [{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}] plain_language: GL-V9 reportedly promoted ubiquitin-proteasome degradation of DLAT.
Complete structured claim and evidence
Disruption of the DLAT–SLC25A39 axis by GL-V9 reportedly depleted mitochondrial glutathione.
GL-V9 → Mammalian mitochondrial reduced-glutathione pool source_derived_draftungraded
Experimental context and source evidence
access_level
abstract_only
compartment
Mitochondrial GSH versus intracellular GSH distinguished by authors
dose
Unknown: full methods unavailable
duration
Unknown: full methods unavailable
endpoint
mitochondrial-gsh-pool
evidence_location
Primary indexed abstract; experiment-specific methods unavailable
experimental_model
Protein interaction/stability, knockdown and compound experiments reported in abstract
exposure
gl-v9
limitations
ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference. Abstract-reported result; specificity and rescue evidence require full text.
nutrient_topic
Topical cross-reference only; no inheritance of another actor's effects. · GSH
organism
Human colorectal cancer models; individual experiments require full-text confirmation
plain_language
Disruption of the DLAT–SLC25A39 axis by GL-V9 reportedly depleted mitochondrial glutathione.
primary_locator
[{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}]
primary_references
https://doi.org/10.1016/j.freeradbiomed.2026.04.133
tissue_or_cell_type
Colorectal cancer models; claim-specific cell line not established from abstract
DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 903–917
AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Protein interaction/stability, knockdown and compound experiments reported in abstract · source_derived_draft · unverified_draft
Disruption of the DLAT–SLC25A39 axis by GL-V9 reportedly depleted mitochondrial glutathione. organism: Human colorectal cancer models; individual experiments require full-text confirmation tissue_or_cell_type: Colorectal cancer models; claim-specific cell line not established from abstract experimental_model: Protein interaction/stability, knockdown and compound experiments reported in abstract compartment: Mitochondrial GSH versus intracellular GSH distinguished by authors dose: Unknown: full methods unavailable duration: Unknown: full methods unavailable primary_references: https://doi.org/10.1016/j.freeradbiomed.2026.04.133 access_level: abstract_only evidence_location: Primary indexed abstract; experiment-specific methods unavailable endpoint: mitochondrial-gsh-pool exposure: gl-v9 limitations: ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference. Abstract-reported result; specificity and rescue evidence require full text. primary_locator: [{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}] plain_language: Disruption of the DLAT–SLC25A39 axis by GL-V9 reportedly depleted mitochondrial glutathione.
Complete structured claim and evidence
GL-V9 reportedly suppressed colorectal-cancer growth in the study models.
GL-V9 → Colorectal cancer growth in study models source_derived_draftungraded
Experimental context and source evidence
access_level
abstract_only
compartment
Mitochondrial GSH versus intracellular GSH distinguished by authors
dose
Unknown: full methods unavailable
duration
Unknown: full methods unavailable
endpoint
crc-growth-model-endpoint
evidence_location
Primary indexed abstract; experiment-specific methods unavailable
experimental_model
Protein interaction/stability, knockdown and compound experiments reported in abstract
exposure
gl-v9
limitations
ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference. The abstract does not establish model-specific dosing, safety or clinical efficacy.
nutrient_topic
Topical cross-reference only; no inheritance of another actor's effects. · GSH
organism
Human colorectal cancer models; individual experiments require full-text confirmation
plain_language
GL-V9 reportedly suppressed colorectal-cancer growth in the study models.
primary_locator
[{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}]
primary_references
https://doi.org/10.1016/j.freeradbiomed.2026.04.133
tissue_or_cell_type
Colorectal cancer models; claim-specific cell line not established from abstract
DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidence · lines 920–934
AI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · supports · Protein interaction/stability, knockdown and compound experiments reported in abstract · source_derived_draft · unverified_draft
GL-V9 reportedly suppressed colorectal-cancer growth in the study models. organism: Human colorectal cancer models; individual experiments require full-text confirmation tissue_or_cell_type: Colorectal cancer models; claim-specific cell line not established from abstract experimental_model: Protein interaction/stability, knockdown and compound experiments reported in abstract compartment: Mitochondrial GSH versus intracellular GSH distinguished by authors dose: Unknown: full methods unavailable duration: Unknown: full methods unavailable primary_references: https://doi.org/10.1016/j.freeradbiomed.2026.04.133 access_level: abstract_only evidence_location: Primary indexed abstract; experiment-specific methods unavailable endpoint: crc-growth-model-endpoint exposure: gl-v9 limitations: ABSTRACT-ONLY CURATION. Full article and supplements were not accessible; assay-specific cell line, dose, timing, controls and sample size remain unverified. No pulmonary-endothelial or clinical-treatment inference. The abstract does not establish model-specific dosing, safety or clinical efficacy. primary_locator: [{"cache": "artifacts/dlat-curation/crc-metadata.json", "json_path": "resultList.result[0].abstractText", "access": "abstract_only"}] plain_language: GL-V9 reportedly suppressed colorectal-cancer growth in the study models.
Complete structured claim and evidence
DELE1 overexpression increased ATF4 in MDA-MB-231 and HCC1806-LM2 cells.
DELE1 overexpression in human breast-cancer cells → Human activating transcription factor 4 / ATF4 source_derived_draftungraded
Experimental context and source evidence
access_level
selected_indexed_full_text_passages
evidence_cache
artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3
experimental_model
MDA-MB-231; HCC1806-LM2
exposure
Overexpression; amount and duration unresolved
limitations
Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium.
organism
Human cultured cells; mouse xenograft host only for colonization endpoint
plain_language
DELE1 overexpression increased ATF4 in MDA-MB-231 and HCC1806-LM2 cells.
primary_locator
https://pmc.ncbi.nlm.nih.gov/articles/PMC12396134/ Figure 4C
primary_references
https://doi.org/10.1158/2159-8290.CD-24-1556
DELE1 bridge: iron sensing and mitochondrial-glutathione-dependent stress signaling · lines 7–16
Targeted primary-literature curation; selected indexed full-text passages, 2026-09-20. · supports · MDA-MB-231; HCC1806-LM2 · source_derived_draft · unverified_draft
DELE1 overexpression increased ATF4 in MDA-MB-231 and HCC1806-LM2 cells. primary_references: https://doi.org/10.1158/2159-8290.CD-24-1556 primary_locator: https://pmc.ncbi.nlm.nih.gov/articles/PMC12396134/ Figure 4C evidence_cache: artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3 access_level: selected_indexed_full_text_passages experimental_model: MDA-MB-231; HCC1806-LM2 organism: Human cultured cells; mouse xenograft host only for colonization endpoint exposure: Overexpression; amount and duration unresolved limitations: Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium. plain_language: DELE1 overexpression increased ATF4 in MDA-MB-231 and HCC1806-LM2 cells.
Complete structured claim and evidence
DELE1 overexpression largely restored lung colonization by SLC25A39-knockout MDA-MB-231 cells.
DELE1 overexpression in human breast-cancer cells → Early lung colonization in SLC25A39-dependent breast-cancer models source_derived_draftungraded
Experimental context and source evidence
access_level
selected_indexed_full_text_passages
evidence_cache
artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3
experimental_model
Human cells injected into mice; 5 mice/group
exposure
500,000 injected cells; timing unresolved
limitations
Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium.
organism
Human cultured cells; mouse xenograft host only for colonization endpoint
plain_language
DELE1 overexpression largely restored lung colonization by SLC25A39-knockout MDA-MB-231 cells.
primary_locator
https://pmc.ncbi.nlm.nih.gov/articles/PMC12396134/ Figure 4D
primary_references
https://doi.org/10.1158/2159-8290.CD-24-1556
DELE1 bridge: iron sensing and mitochondrial-glutathione-dependent stress signaling · lines 19–28
Targeted primary-literature curation; selected indexed full-text passages, 2026-09-20. · supports · Human cells injected into mice; 5 mice/group · source_derived_draft · unverified_draft
DELE1 overexpression largely restored lung colonization by SLC25A39-knockout MDA-MB-231 cells. primary_references: https://doi.org/10.1158/2159-8290.CD-24-1556 primary_locator: https://pmc.ncbi.nlm.nih.gov/articles/PMC12396134/ Figure 4D evidence_cache: artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3 access_level: selected_indexed_full_text_passages experimental_model: Human cells injected into mice; 5 mice/group organism: Human cultured cells; mouse xenograft host only for colonization endpoint exposure: 500,000 injected cells; timing unresolved limitations: Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium. plain_language: DELE1 overexpression largely restored lung colonization by SLC25A39-knockout MDA-MB-231 cells.
Complete structured claim and evidence
SLC25A39 knockout attenuated hypoxic ATF4 induction in MDA-MB-231 cells.
SLC25A39 knockout in MDA-MB-231 cells → Human activating transcription factor 4 / ATF4 source_derived_draftungraded
Experimental context and source evidence
access_level
selected_indexed_full_text_passages
evidence_cache
artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3
experimental_model
MDA-MB-231
exposure
1% oxygen; 12/24 hours
limitations
Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium.
organism
Human cultured cells; mouse xenograft host only for colonization endpoint
plain_language
SLC25A39 knockout attenuated hypoxic ATF4 induction in MDA-MB-231 cells.
primary_locator
https://pmc.ncbi.nlm.nih.gov/articles/PMC12396134/ Figure 4E
primary_references
https://doi.org/10.1158/2159-8290.CD-24-1556
DELE1 bridge: iron sensing and mitochondrial-glutathione-dependent stress signaling · lines 31–40
Targeted primary-literature curation; selected indexed full-text passages, 2026-09-20. · supports · MDA-MB-231 · source_derived_draft · unverified_draft
SLC25A39 knockout attenuated hypoxic ATF4 induction in MDA-MB-231 cells. primary_references: https://doi.org/10.1158/2159-8290.CD-24-1556 primary_locator: https://pmc.ncbi.nlm.nih.gov/articles/PMC12396134/ Figure 4E evidence_cache: artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3 access_level: selected_indexed_full_text_passages experimental_model: MDA-MB-231 organism: Human cultured cells; mouse xenograft host only for colonization endpoint exposure: 1% oxygen; 12/24 hours limitations: Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium. plain_language: SLC25A39 knockout attenuated hypoxic ATF4 induction in MDA-MB-231 cells.
Complete structured claim and evidence
SLC25A39 knockout attenuated hypoxia-associated DELE1 cleavage in HEK293T cells.
SLC25A39 knockout in endogenous DELE1-HA HEK293T cells → Human DELE1 cleavage readout source_derived_draftungraded
Experimental context and source evidence
access_level
selected_indexed_full_text_passages
evidence_cache
artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3
experimental_model
Endogenous DELE1-HA HEK293T
exposure
1% oxygen; exact panel times unresolved
limitations
Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium.
organism
Human cultured cells; mouse xenograft host only for colonization endpoint
plain_language
SLC25A39 knockout attenuated hypoxia-associated DELE1 cleavage in HEK293T cells.
primary_locator
https://pmc.ncbi.nlm.nih.gov/articles/PMC12396134/ Figure 4F
primary_references
https://doi.org/10.1158/2159-8290.CD-24-1556
DELE1 bridge: iron sensing and mitochondrial-glutathione-dependent stress signaling · lines 43–52
Targeted primary-literature curation; selected indexed full-text passages, 2026-09-20. · supports · Endogenous DELE1-HA HEK293T · source_derived_draft · unverified_draft
SLC25A39 knockout attenuated hypoxia-associated DELE1 cleavage in HEK293T cells. primary_references: https://doi.org/10.1158/2159-8290.CD-24-1556 primary_locator: https://pmc.ncbi.nlm.nih.gov/articles/PMC12396134/ Figure 4F evidence_cache: artifacts/discovery-research/round2-sources/primary-mechanism-passages.json; SHA256 81c0207494f0b2a22fd0af0d70528a5114dfd74367dd99f967f4ada68c53e8c3 access_level: selected_indexed_full_text_passages experimental_model: Endogenous DELE1-HA HEK293T organism: Human cultured cells; mouse xenograft host only for colonization endpoint exposure: 1% oxygen; exact panel times unresolved limitations: Selected indexed primary full-text passages reviewed; supplements not independently inspected in this round. These records do not demonstrate iron-chelation rescue of SLC25A39 loss, clinical benefit, or transfer to pulmonary endothelium. plain_language: SLC25A39 knockout attenuated hypoxia-associated DELE1 cleavage in HEK293T cells.
Complete structured claim and evidence
SLC25A39 knockdown increased ER-mitochondria contacts in HeLa MERBiT cells.
SLC25A39 knockdown in HeLa cells → ER-mitochondria contacts in human cells source_derived_draftungraded
Experimental context and source evidence
access_level
selected_primary_main_text_and_legends; cached web/indexed passages, not complete supplement review
evidence_cache
artifacts/discovery-research/round4-sources/contact-2025-indexed-passages.json; SHA256 9222f94099520a9b5e9ee8b7f30a1b4ae261735d37462b13d7ca3d0ecc8792d6
experimental_model
HeLa; MERBiT reporter derivative where stated
exposure
3-day siRNA exposure; MERBiT luminescence; dose unresolved
limitations
Selected primary main-text Results and figure legends reviewed; supplementary images not independently inspected. These two papers share authors and are not independent replication. They do not test whether SLC25A39-loss-induced contacts increase HMOX2-dependent iron delivery. ICP-MS measures total iron, not labile iron or transport flux. Contact loss affecting an outcome does not establish that increasing contacts increases it. Ubiquitination/activity readouts do not establish direct enzymatic activation or the outer-membrane iron transport machinery. No clinical or pulmonary-endothelial effect is inferred.
organism
Human
primary_locator
Figure 2f and Results: Induction of mitochondrial ROS
primary_references
https://doi.org/10.1038/s41467-025-56666-4
Glutathione, ER-mitochondria contacts, and iron: observed components · lines 6–14
Targeted primary-literature curation, 2026-09-20. DOIs 10.1038/s41467-025-56666-4 and 10.1038/s41556-026-01974-0. · supports · Human HeLa cells · source_derived_draft · unverified_draft
SLC25A39 knockdown increased ER-mitochondria contacts in HeLa MERBiT cells. primary_references: https://doi.org/10.1038/s41467-025-56666-4 primary_locator: Figure 2f and Results: Induction of mitochondrial ROS evidence_cache: artifacts/discovery-research/round4-sources/contact-2025-indexed-passages.json; SHA256 9222f94099520a9b5e9ee8b7f30a1b4ae261735d37462b13d7ca3d0ecc8792d6 access_level: selected_primary_main_text_and_legends; cached web/indexed passages, not complete supplement review organism: Human experimental_model: HeLa; MERBiT reporter derivative where stated exposure: 3-day siRNA exposure; MERBiT luminescence; dose unresolved limitations: Selected primary main-text Results and figure legends reviewed; supplementary images not independently inspected. These two papers share authors and are not independent replication. They do not test whether SLC25A39-loss-induced contacts increase HMOX2-dependent iron delivery. ICP-MS measures total iron, not labile iron or transport flux. Contact loss affecting an outcome does not establish that increasing contacts increases it. Ubiquitination/activity readouts do not establish direct enzymatic activation or the outer-membrane iron transport machinery. No clinical or pulmonary-endothelial effect is inferred.
Complete structured claim and evidence
RMDN3 knockdown reduced the increased contacts observed during SLC25A39 knockdown.
RMDN3 knockdown in human cells → ER-mitochondria contacts in human cells source_derived_draftungraded
Experimental context and source evidence
access_level
selected_primary_main_text_and_legends; cached web/indexed passages, not complete supplement review
evidence_cache
artifacts/discovery-research/round4-sources/contact-2025-indexed-passages.json; SHA256 9222f94099520a9b5e9ee8b7f30a1b4ae261735d37462b13d7ca3d0ecc8792d6
experimental_model
HeLa; MERBiT reporter derivative where stated
exposure
HeLa MERBiT cells; combined knockdown; exact supplementary timing/dose unresolved
limitations
Selected primary main-text Results and figure legends reviewed; supplementary images not independently inspected. These two papers share authors and are not independent replication. They do not test whether SLC25A39-loss-induced contacts increase HMOX2-dependent iron delivery. ICP-MS measures total iron, not labile iron or transport flux. Contact loss affecting an outcome does not establish that increasing contacts increases it. Ubiquitination/activity readouts do not establish direct enzymatic activation or the outer-membrane iron transport machinery. No clinical or pulmonary-endothelial effect is inferred.
organism
Human
primary_locator
Results citing Supplementary Figure 4a
primary_references
https://doi.org/10.1038/s41467-025-56666-4
Glutathione, ER-mitochondria contacts, and iron: observed components · lines 17–25
Targeted primary-literature curation, 2026-09-20. DOIs 10.1038/s41467-025-56666-4 and 10.1038/s41556-026-01974-0. · supports · Human HeLa cells · source_derived_draft · unverified_draft
RMDN3 knockdown reduced the increased contacts observed during SLC25A39 knockdown. primary_references: https://doi.org/10.1038/s41467-025-56666-4 primary_locator: Results citing Supplementary Figure 4a evidence_cache: artifacts/discovery-research/round4-sources/contact-2025-indexed-passages.json; SHA256 9222f94099520a9b5e9ee8b7f30a1b4ae261735d37462b13d7ca3d0ecc8792d6 access_level: selected_primary_main_text_and_legends; cached web/indexed passages, not complete supplement review organism: Human experimental_model: HeLa; MERBiT reporter derivative where stated exposure: HeLa MERBiT cells; combined knockdown; exact supplementary timing/dose unresolved limitations: Selected primary main-text Results and figure legends reviewed; supplementary images not independently inspected. These two papers share authors and are not independent replication. They do not test whether SLC25A39-loss-induced contacts increase HMOX2-dependent iron delivery. ICP-MS measures total iron, not labile iron or transport flux. Contact loss affecting an outcome does not establish that increasing contacts increases it. Ubiquitination/activity readouts do not establish direct enzymatic activation or the outer-membrane iron transport machinery. No clinical or pulmonary-endothelial effect is inferred.
Complete structured claim and evidence
VAPB knockdown reduced the increased contacts observed during SLC25A39 knockdown.
VAPB knockdown in human cells → ER-mitochondria contacts in human cells source_derived_draftungraded
Experimental context and source evidence
access_level
selected_primary_main_text_and_legends; cached web/indexed passages, not complete supplement review
evidence_cache
artifacts/discovery-research/round4-sources/contact-2025-indexed-passages.json; SHA256 9222f94099520a9b5e9ee8b7f30a1b4ae261735d37462b13d7ca3d0ecc8792d6
experimental_model
HeLa; MERBiT reporter derivative where stated
exposure
HeLa MERBiT cells; combined knockdown; exact supplementary timing/dose unresolved
limitations
Selected primary main-text Results and figure legends reviewed; supplementary images not independently inspected. These two papers share authors and are not independent replication. They do not test whether SLC25A39-loss-induced contacts increase HMOX2-dependent iron delivery. ICP-MS measures total iron, not labile iron or transport flux. Contact loss affecting an outcome does not establish that increasing contacts increases it. Ubiquitination/activity readouts do not establish direct enzymatic activation or the outer-membrane iron transport machinery. No clinical or pulmonary-endothelial effect is inferred.
organism
Human
primary_locator
Results citing Supplementary Figure 4a
primary_references
https://doi.org/10.1038/s41467-025-56666-4
Glutathione, ER-mitochondria contacts, and iron: observed components · lines 28–36
Targeted primary-literature curation, 2026-09-20. DOIs 10.1038/s41467-025-56666-4 and 10.1038/s41556-026-01974-0. · supports · Human HeLa cells · source_derived_draft · unverified_draft
VAPB knockdown reduced the increased contacts observed during SLC25A39 knockdown. primary_references: https://doi.org/10.1038/s41467-025-56666-4 primary_locator: Results citing Supplementary Figure 4a evidence_cache: artifacts/discovery-research/round4-sources/contact-2025-indexed-passages.json; SHA256 9222f94099520a9b5e9ee8b7f30a1b4ae261735d37462b13d7ca3d0ecc8792d6 access_level: selected_primary_main_text_and_legends; cached web/indexed passages, not complete supplement review organism: Human experimental_model: HeLa; MERBiT reporter derivative where stated exposure: HeLa MERBiT cells; combined knockdown; exact supplementary timing/dose unresolved limitations: Selected primary main-text Results and figure legends reviewed; supplementary images not independently inspected. These two papers share authors and are not independent replication. They do not test whether SLC25A39-loss-induced contacts increase HMOX2-dependent iron delivery. ICP-MS measures total iron, not labile iron or transport flux. Contact loss affecting an outcome does not establish that increasing contacts increases it. Ubiquitination/activity readouts do not establish direct enzymatic activation or the outer-membrane iron transport machinery. No clinical or pulmonary-endothelial effect is inferred.
Complete structured claim and evidence
RMDN3 knockdown reduced HeLa cell viability during SLC25A39 silencing.
RMDN3 knockdown in human cells → HeLa cell viability readout source_derived_draftungraded
Experimental context and source evidence
access_level
selected_primary_main_text_and_legends; cached web/indexed passages, not complete supplement review
evidence_cache
artifacts/discovery-research/round4-sources/contact-2025-indexed-passages.json; SHA256 9222f94099520a9b5e9ee8b7f30a1b4ae261735d37462b13d7ca3d0ecc8792d6
experimental_model
HeLa; MERBiT reporter derivative where stated
exposure
Combined silencing; CCK-8 viability assay; exact supplementary dose and timing unresolved
limitations
Selected primary main-text Results and figure legends reviewed; supplementary images not independently inspected. These two papers share authors and are not independent replication. They do not test whether SLC25A39-loss-induced contacts increase HMOX2-dependent iron delivery. ICP-MS measures total iron, not labile iron or transport flux. Contact loss affecting an outcome does not establish that increasing contacts increases it. Ubiquitination/activity readouts do not establish direct enzymatic activation or the outer-membrane iron transport machinery. No clinical or pulmonary-endothelial effect is inferred.
organism
Human
primary_locator
Results: Disruption of mitochondrial ROS-derived MERCs; Supplementary Figure 5a
primary_references
https://doi.org/10.1038/s41467-025-56666-4
Glutathione, ER-mitochondria contacts, and iron: observed components · lines 39–47
Targeted primary-literature curation, 2026-09-20. DOIs 10.1038/s41467-025-56666-4 and 10.1038/s41556-026-01974-0. · supports · Human HeLa cells · source_derived_draft · unverified_draft
RMDN3 knockdown reduced HeLa cell viability during SLC25A39 silencing. primary_references: https://doi.org/10.1038/s41467-025-56666-4 primary_locator: Results: Disruption of mitochondrial ROS-derived MERCs; Supplementary Figure 5a evidence_cache: artifacts/discovery-research/round4-sources/contact-2025-indexed-passages.json; SHA256 9222f94099520a9b5e9ee8b7f30a1b4ae261735d37462b13d7ca3d0ecc8792d6 access_level: selected_primary_main_text_and_legends; cached web/indexed passages, not complete supplement review organism: Human experimental_model: HeLa; MERBiT reporter derivative where stated exposure: Combined silencing; CCK-8 viability assay; exact supplementary dose and timing unresolved limitations: Selected primary main-text Results and figure legends reviewed; supplementary images not independently inspected. These two papers share authors and are not independent replication. They do not test whether SLC25A39-loss-induced contacts increase HMOX2-dependent iron delivery. ICP-MS measures total iron, not labile iron or transport flux. Contact loss affecting an outcome does not establish that increasing contacts increases it. Ubiquitination/activity readouts do not establish direct enzymatic activation or the outer-membrane iron transport machinery. No clinical or pulmonary-endothelial effect is inferred.
Complete structured claim and evidence
The published human K562 dual-targeting screen reports SLC16A11/SLC25A39 genetic interaction pi=0.154314615559463 with significance value 0.0185030434905457 under Glc15. This is a relative-fitness interaction estimate, not restoration of mitochondrial glutathione.
Combined SLC16A11 and SLC25A39 targeting in human K562 screen → Human K562 pooled screen relative fitness source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Human K562 pooled CRISPR screen; two batches; paired SaCas9/SpCas9 guides
exposure
15-day growth screen; 25 mM glucose, 1 mM sodium pyruvate; 10% dialyzed FBS and 50 microgram/mL uridine.
limitations
Positive pi describes departure from an additive fitness expectation, not positive regulation between wild-type proteins. All four pi estimates are below the authors absolute pi >0.25 large-effect cutoff. Glucose significance value is below 0.02; other conditions are not. These are authors reported BH-adjusted values according to their archived pi_score code, not new p-values. Guide constructs are not independent biological replicates. No new genotype-by-environment significance test was performed.
organism
Human
primary_locator
Supplementary Data 3, Glc15_piscore and Glc15_pvalue, BD40 (row SLC25A39, column SLC16A11); Supplementary Data 4 All_Data_Sig_0.02 includes the glucose pair.
primary_references
https://doi.org/10.1038/s41467-022-30126-9
trigger_kind
machinery_impairment Imported condition classification; unverified.
SLC16A11 and mitochondrial glutathione: published screen connection and transport evidence · lines 6–12
Primary sources 2022 and 2017, plus labelled descriptive reanalysis on 2026-09-20. · supports · Human K562 pooled CRISPR screen; two batches; paired SaCas9/SpCas9 guides · source_derived_draft · unverified_draft
The published human K562 dual-targeting screen reports SLC16A11/SLC25A39 genetic interaction pi=0.154314615559463 with significance value 0.0185030434905457 under Glc15. This is a relative-fitness interaction estimate, not restoration of mitochondrial glutathione. primary_references: https://doi.org/10.1038/s41467-022-30126-9 primary_locator: Supplementary Data 3, Glc15_piscore and Glc15_pvalue, BD40 (row SLC25A39, column SLC16A11); Supplementary Data 4 All_Data_Sig_0.02 includes the glucose pair. organism: Human experimental_model: Human K562 pooled CRISPR screen; two batches; paired SaCas9/SpCas9 guides exposure: 15-day growth screen; 25 mM glucose, 1 mM sodium pyruvate; 10% dialyzed FBS and 50 microgram/mL uridine. limitations: Positive pi describes departure from an additive fitness expectation, not positive regulation between wild-type proteins. All four pi estimates are below the authors absolute pi >0.25 large-effect cutoff. Glucose significance value is below 0.02; other conditions are not. These are authors reported BH-adjusted values according to their archived pi_score code, not new p-values. Guide constructs are not independent biological replicates. No new genotype-by-environment significance test was performed.
Complete structured claim and evidence
The published human K562 dual-targeting screen reports SLC16A11/SLC25A39 genetic interaction pi=0.0272123713337914 with significance value 0.578178616323455 under Gal15. This is a relative-fitness interaction estimate, not restoration of mitochondrial glutathione.
Combined SLC16A11 and SLC25A39 targeting in human K562 screen → Human K562 pooled screen relative fitness source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Human K562 pooled CRISPR screen; two batches; paired SaCas9/SpCas9 guides
exposure
15-day growth screen; 25 mM galactose replacing glucose, 1 mM sodium pyruvate; 10% dialyzed FBS and 50 microgram/mL uridine.
limitations
Positive pi describes departure from an additive fitness expectation, not positive regulation between wild-type proteins. All four pi estimates are below the authors absolute pi >0.25 large-effect cutoff. Glucose significance value is below 0.02; other conditions are not. These are authors reported BH-adjusted values according to their archived pi_score code, not new p-values. Guide constructs are not independent biological replicates. No new genotype-by-environment significance test was performed.
organism
Human
primary_locator
Supplementary Data 3, Gal15_piscore and Gal15_pvalue, BD40 (row SLC25A39, column SLC16A11); Supplementary Data 4 All_Data_Sig_0.02 includes the glucose pair.
primary_references
https://doi.org/10.1038/s41467-022-30126-9
trigger_kind
machinery_impairment Imported condition classification; unverified.
SLC16A11 and mitochondrial glutathione: published screen connection and transport evidence · lines 15–21
Primary sources 2022 and 2017, plus labelled descriptive reanalysis on 2026-09-20. · supports · Human K562 pooled CRISPR screen; two batches; paired SaCas9/SpCas9 guides · source_derived_draft · unverified_draft
The published human K562 dual-targeting screen reports SLC16A11/SLC25A39 genetic interaction pi=0.0272123713337914 with significance value 0.578178616323455 under Gal15. This is a relative-fitness interaction estimate, not restoration of mitochondrial glutathione. primary_references: https://doi.org/10.1038/s41467-022-30126-9 primary_locator: Supplementary Data 3, Gal15_piscore and Gal15_pvalue, BD40 (row SLC25A39, column SLC16A11); Supplementary Data 4 All_Data_Sig_0.02 includes the glucose pair. organism: Human experimental_model: Human K562 pooled CRISPR screen; two batches; paired SaCas9/SpCas9 guides exposure: 15-day growth screen; 25 mM galactose replacing glucose, 1 mM sodium pyruvate; 10% dialyzed FBS and 50 microgram/mL uridine. limitations: Positive pi describes departure from an additive fitness expectation, not positive regulation between wild-type proteins. All four pi estimates are below the authors absolute pi >0.25 large-effect cutoff. Glucose significance value is below 0.02; other conditions are not. These are authors reported BH-adjusted values according to their archived pi_score code, not new p-values. Guide constructs are not independent biological replicates. No new genotype-by-environment significance test was performed.
Complete structured claim and evidence
The published human K562 dual-targeting screen reports SLC16A11/SLC25A39 genetic interaction pi=0.0805858670811976 with significance value 0.612290402312043 under Anti15. This is a relative-fitness interaction estimate, not restoration of mitochondrial glutathione.
Combined SLC16A11 and SLC25A39 targeting in human K562 screen → Human K562 pooled screen relative fitness source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Human K562 pooled CRISPR screen; two batches; paired SaCas9/SpCas9 guides
exposure
15-day growth screen; 25 mM glucose, 1 mM sodium pyruvate, 100 nM antimycin; 10% dialyzed FBS and 50 microgram/mL uridine.
limitations
Positive pi describes departure from an additive fitness expectation, not positive regulation between wild-type proteins. All four pi estimates are below the authors absolute pi >0.25 large-effect cutoff. Glucose significance value is below 0.02; other conditions are not. These are authors reported BH-adjusted values according to their archived pi_score code, not new p-values. Guide constructs are not independent biological replicates. No new genotype-by-environment significance test was performed.
organism
Human
primary_locator
Supplementary Data 3, Anti15_piscore and Anti15_pvalue, BD40 (row SLC25A39, column SLC16A11); Supplementary Data 4 All_Data_Sig_0.02 includes the glucose pair.
primary_references
https://doi.org/10.1038/s41467-022-30126-9
trigger_kind
machinery_impairment Imported condition classification; unverified.
SLC16A11 and mitochondrial glutathione: published screen connection and transport evidence · lines 24–30
Primary sources 2022 and 2017, plus labelled descriptive reanalysis on 2026-09-20. · supports · Human K562 pooled CRISPR screen; two batches; paired SaCas9/SpCas9 guides · source_derived_draft · unverified_draft
The published human K562 dual-targeting screen reports SLC16A11/SLC25A39 genetic interaction pi=0.0805858670811976 with significance value 0.612290402312043 under Anti15. This is a relative-fitness interaction estimate, not restoration of mitochondrial glutathione. primary_references: https://doi.org/10.1038/s41467-022-30126-9 primary_locator: Supplementary Data 3, Anti15_piscore and Anti15_pvalue, BD40 (row SLC25A39, column SLC16A11); Supplementary Data 4 All_Data_Sig_0.02 includes the glucose pair. organism: Human experimental_model: Human K562 pooled CRISPR screen; two batches; paired SaCas9/SpCas9 guides exposure: 15-day growth screen; 25 mM glucose, 1 mM sodium pyruvate, 100 nM antimycin; 10% dialyzed FBS and 50 microgram/mL uridine. limitations: Positive pi describes departure from an additive fitness expectation, not positive regulation between wild-type proteins. All four pi estimates are below the authors absolute pi >0.25 large-effect cutoff. Glucose significance value is below 0.02; other conditions are not. These are authors reported BH-adjusted values according to their archived pi_score code, not new p-values. Guide constructs are not independent biological replicates. No new genotype-by-environment significance test was performed.
Complete structured claim and evidence
The published human K562 dual-targeting screen reports SLC16A11/SLC25A39 genetic interaction pi=0.155012680942449 with significance value 0.0621187730457448 under Pyr15. This is a relative-fitness interaction estimate, not restoration of mitochondrial glutathione.
Combined SLC16A11 and SLC25A39 targeting in human K562 screen → Human K562 pooled screen relative fitness source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Human K562 pooled CRISPR screen; two batches; paired SaCas9/SpCas9 guides
exposure
15-day growth screen; 25 mM glucose, without added sodium pyruvate; 10% dialyzed FBS and 50 microgram/mL uridine.
limitations
Positive pi describes departure from an additive fitness expectation, not positive regulation between wild-type proteins. All four pi estimates are below the authors absolute pi >0.25 large-effect cutoff. Glucose significance value is below 0.02; other conditions are not. These are authors reported BH-adjusted values according to their archived pi_score code, not new p-values. Guide constructs are not independent biological replicates. No new genotype-by-environment significance test was performed.
organism
Human
primary_locator
Supplementary Data 3, Pyr15_piscore and Pyr15_pvalue, BD40 (row SLC25A39, column SLC16A11); Supplementary Data 4 All_Data_Sig_0.02 includes the glucose pair.
primary_references
https://doi.org/10.1038/s41467-022-30126-9
trigger_kind
machinery_impairment Imported condition classification; unverified.
SLC16A11 and mitochondrial glutathione: published screen connection and transport evidence · lines 33–39
Primary sources 2022 and 2017, plus labelled descriptive reanalysis on 2026-09-20. · supports · Human K562 pooled CRISPR screen; two batches; paired SaCas9/SpCas9 guides · source_derived_draft · unverified_draft
The published human K562 dual-targeting screen reports SLC16A11/SLC25A39 genetic interaction pi=0.155012680942449 with significance value 0.0621187730457448 under Pyr15. This is a relative-fitness interaction estimate, not restoration of mitochondrial glutathione. primary_references: https://doi.org/10.1038/s41467-022-30126-9 primary_locator: Supplementary Data 3, Pyr15_piscore and Pyr15_pvalue, BD40 (row SLC25A39, column SLC16A11); Supplementary Data 4 All_Data_Sig_0.02 includes the glucose pair. organism: Human experimental_model: Human K562 pooled CRISPR screen; two batches; paired SaCas9/SpCas9 guides exposure: 15-day growth screen; 25 mM glucose, without added sodium pyruvate; 10% dialyzed FBS and 50 microgram/mL uridine. limitations: Positive pi describes departure from an additive fitness expectation, not positive regulation between wild-type proteins. All four pi estimates are below the authors absolute pi >0.25 large-effect cutoff. Glucose significance value is below 0.02; other conditions are not. These are authors reported BH-adjusted values according to their archived pi_score code, not new p-values. Guide constructs are not independent biological replicates. No new genotype-by-environment significance test was performed.
Complete structured claim and evidence
HEK293T cells expressing reference SLC16A11 showed approximately 45 percent higher pyruvate influx rate than empty-vector controls in the reported assay.
Reference SLC16A11 expression in human HEK293T cells → Human HEK293T pyruvate influx assay source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human HEK293T cells expressing human reference SLC16A11-V5 and pyronic FRET sensor
exposure
Addition and withdrawal of 0.4 mM pyruvate; neutral pH; Figure 3E reports n=11 and P<0.05. Methods: 2 microgram pyronic and 2 microgram transporter/empty-vector plasmid, transfected 24 hours after plating on coverslips 72 hours before assay.
limitations
Selected primary main-text results, figure legend and methods reviewed through indexed PMC passages; supplements not independently reviewed. Difference was observed at neutral pH, not at acidic pH. This is not a K562 experiment and does not establish the mechanism of the genetic interaction. SLC16A11 has intracellular and cell-surface pools; pyruvate transport direction depends on gradients.
organism
Human
primary_locator
Results: SLC16A11 is a H+-coupled monocarboxylate transporter; Figure 3D-E; pyruvate transport methods.
primary_references
https://doi.org/10.1016/j.cell.2017.06.011
SLC16A11 and mitochondrial glutathione: published screen connection and transport evidence · lines 42–48
Primary sources 2022 and 2017, plus labelled descriptive reanalysis on 2026-09-20. · supports · Human HEK293T cells expressing human reference SLC16A11-V5 and pyronic FRET sensor · source_derived_draft · unverified_draft
HEK293T cells expressing reference SLC16A11 showed approximately 45 percent higher pyruvate influx rate than empty-vector controls in the reported assay. primary_references: https://doi.org/10.1016/j.cell.2017.06.011 primary_locator: Results: SLC16A11 is a H+-coupled monocarboxylate transporter; Figure 3D-E; pyruvate transport methods. organism: Human experimental_model: Human HEK293T cells expressing human reference SLC16A11-V5 and pyronic FRET sensor exposure: Addition and withdrawal of 0.4 mM pyruvate; neutral pH; Figure 3E reports n=11 and P<0.05. Methods: 2 microgram pyronic and 2 microgram transporter/empty-vector plasmid, transfected 24 hours after plating on coverslips 72 hours before assay. limitations: Selected primary main-text results, figure legend and methods reviewed through indexed PMC passages; supplements not independently reviewed. Difference was observed at neutral pH, not at acidic pH. This is not a K562 experiment and does not establish the mechanism of the genetic interaction. SLC16A11 has intracellular and cell-surface pools; pyruvate transport direction depends on gradients.
Complete structured claim and evidence
HEK293T cells expressing reference SLC16A11 showed approximately 45 percent higher pyruvate efflux rate than empty-vector controls in the reported assay.
Reference SLC16A11 expression in human HEK293T cells → Human HEK293T pyruvate efflux assay source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human HEK293T cells expressing human reference SLC16A11-V5 and pyronic FRET sensor
exposure
Addition and withdrawal of 0.4 mM pyruvate; neutral pH; Figure 3E reports n=11 and P<0.05. Methods: 2 microgram pyronic and 2 microgram transporter/empty-vector plasmid, transfected 24 hours after plating on coverslips 72 hours before assay.
limitations
Selected primary main-text results, figure legend and methods reviewed through indexed PMC passages; supplements not independently reviewed. Difference was observed at neutral pH, not at acidic pH. This is not a K562 experiment and does not establish the mechanism of the genetic interaction. SLC16A11 has intracellular and cell-surface pools; pyruvate transport direction depends on gradients.
organism
Human
primary_locator
Results: SLC16A11 is a H+-coupled monocarboxylate transporter; Figure 3D-E; pyruvate transport methods.
primary_references
https://doi.org/10.1016/j.cell.2017.06.011
SLC16A11 and mitochondrial glutathione: published screen connection and transport evidence · lines 51–57
Primary sources 2022 and 2017, plus labelled descriptive reanalysis on 2026-09-20. · supports · Human HEK293T cells expressing human reference SLC16A11-V5 and pyronic FRET sensor · source_derived_draft · unverified_draft
HEK293T cells expressing reference SLC16A11 showed approximately 45 percent higher pyruvate efflux rate than empty-vector controls in the reported assay. primary_references: https://doi.org/10.1016/j.cell.2017.06.011 primary_locator: Results: SLC16A11 is a H+-coupled monocarboxylate transporter; Figure 3D-E; pyruvate transport methods. organism: Human experimental_model: Human HEK293T cells expressing human reference SLC16A11-V5 and pyronic FRET sensor exposure: Addition and withdrawal of 0.4 mM pyruvate; neutral pH; Figure 3E reports n=11 and P<0.05. Methods: 2 microgram pyronic and 2 microgram transporter/empty-vector plasmid, transfected 24 hours after plating on coverslips 72 hours before assay. limitations: Selected primary main-text results, figure legend and methods reviewed through indexed PMC passages; supplements not independently reviewed. Difference was observed at neutral pH, not at acidic pH. This is not a K562 experiment and does not establish the mechanism of the genetic interaction. SLC16A11 has intracellular and cell-surface pools; pyruvate transport direction depends on gradients.
Complete structured claim and evidence
Wild-type APT2 re-expression lowered GPX4 protein in APT2-depleted A375 cells.
Human A375 APT2 knockdown with HA-APT2 WT re-expression → GPX4 protein abundance in human cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs
exposure
HA-tagged rescue constructs; Figure 6j: 48-hour RSL3 challenge, n=3 independent experiments. Exact RSL3 concentrations follow the figure dose response and are not inferred here.
limitations
C2S affects APT2 palmitoylation/localization and is not identical to the S122A catalytic-site perturbation. Null comparisons do not prove equivalence. No sulforaphane or solasonine tested in this rescue experiment.
organism
Human
primary_locator
Figure 6i-j; Results: Inhibition of APT2 suppresses ferroptosis.
primary_references
https://doi.org/10.1038/s41467-025-56344-5
trigger_kind
machinery_impairment Imported condition classification; unverified.
APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 6–12
Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs · source_derived_draft · unverified_draft
Wild-type APT2 re-expression lowered GPX4 protein in APT2-depleted A375 cells. primary_references: https://doi.org/10.1038/s41467-025-56344-5 primary_locator: Figure 6i-j; Results: Inhibition of APT2 suppresses ferroptosis. organism: Human experimental_model: Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs exposure: HA-tagged rescue constructs; Figure 6j: 48-hour RSL3 challenge, n=3 independent experiments. Exact RSL3 concentrations follow the figure dose response and are not inferred here. limitations: C2S affects APT2 palmitoylation/localization and is not identical to the S122A catalytic-site perturbation. Null comparisons do not prove equivalence. No sulforaphane or solasonine tested in this rescue experiment.
Complete structured claim and evidence
Wild-type APT2 re-expression restored RSL3 susceptibility in APT2-depleted A375 cells.
Human A375 APT2 knockdown with HA-APT2 WT re-expression → RSL3-induced cell death in A375 cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs
exposure
HA-tagged rescue constructs; Figure 6j: 48-hour RSL3 challenge, n=3 independent experiments. Exact RSL3 concentrations follow the figure dose response and are not inferred here.
limitations
C2S affects APT2 palmitoylation/localization and is not identical to the S122A catalytic-site perturbation. Null comparisons do not prove equivalence. No sulforaphane or solasonine tested in this rescue experiment.
organism
Human
primary_locator
Figure 6i-j; Results: Inhibition of APT2 suppresses ferroptosis.
primary_references
https://doi.org/10.1038/s41467-025-56344-5
trigger_kind
machinery_impairment Imported condition classification; unverified.
APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 15–21
Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs · source_derived_draft · unverified_draft
Wild-type APT2 re-expression restored RSL3 susceptibility in APT2-depleted A375 cells. primary_references: https://doi.org/10.1038/s41467-025-56344-5 primary_locator: Figure 6i-j; Results: Inhibition of APT2 suppresses ferroptosis. organism: Human experimental_model: Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs exposure: HA-tagged rescue constructs; Figure 6j: 48-hour RSL3 challenge, n=3 independent experiments. Exact RSL3 concentrations follow the figure dose response and are not inferred here. limitations: C2S affects APT2 palmitoylation/localization and is not identical to the S122A catalytic-site perturbation. Null comparisons do not prove equivalence. No sulforaphane or solasonine tested in this rescue experiment.
Complete structured claim and evidence
C2S APT2 re-expression did not reproduce the wild-type reduction in GPX4 protein in APT2-depleted A375 cells.
Human A375 APT2 knockdown with HA-APT2 C2S re-expression → GPX4 protein abundance in human cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs
exposure
HA-tagged rescue constructs; Figure 6j: 48-hour RSL3 challenge, n=3 independent experiments. Exact RSL3 concentrations follow the figure dose response and are not inferred here.
limitations
C2S affects APT2 palmitoylation/localization and is not identical to the S122A catalytic-site perturbation. Null comparisons do not prove equivalence. No sulforaphane or solasonine tested in this rescue experiment.
organism
Human
primary_locator
Figure 6i-j; Results: Inhibition of APT2 suppresses ferroptosis.
primary_references
https://doi.org/10.1038/s41467-025-56344-5
trigger_kind
machinery_impairment Imported condition classification; unverified.
APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 24–30
Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs · source_derived_draft · unverified_draft
C2S APT2 re-expression did not reproduce the wild-type reduction in GPX4 protein in APT2-depleted A375 cells. primary_references: https://doi.org/10.1038/s41467-025-56344-5 primary_locator: Figure 6i-j; Results: Inhibition of APT2 suppresses ferroptosis. organism: Human experimental_model: Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs exposure: HA-tagged rescue constructs; Figure 6j: 48-hour RSL3 challenge, n=3 independent experiments. Exact RSL3 concentrations follow the figure dose response and are not inferred here. limitations: C2S affects APT2 palmitoylation/localization and is not identical to the S122A catalytic-site perturbation. Null comparisons do not prove equivalence. No sulforaphane or solasonine tested in this rescue experiment.
Complete structured claim and evidence
C2S APT2 re-expression did not reproduce wild-type restoration of RSL3 susceptibility in APT2-depleted A375 cells.
Human A375 APT2 knockdown with HA-APT2 C2S re-expression → RSL3-induced cell death in A375 cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs
exposure
HA-tagged rescue constructs; Figure 6j: 48-hour RSL3 challenge, n=3 independent experiments. Exact RSL3 concentrations follow the figure dose response and are not inferred here.
limitations
C2S affects APT2 palmitoylation/localization and is not identical to the S122A catalytic-site perturbation. Null comparisons do not prove equivalence. No sulforaphane or solasonine tested in this rescue experiment.
organism
Human
primary_locator
Figure 6i-j; Results: Inhibition of APT2 suppresses ferroptosis.
primary_references
https://doi.org/10.1038/s41467-025-56344-5
trigger_kind
machinery_impairment Imported condition classification; unverified.
APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 33–39
Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs · source_derived_draft · unverified_draft
C2S APT2 re-expression did not reproduce wild-type restoration of RSL3 susceptibility in APT2-depleted A375 cells. primary_references: https://doi.org/10.1038/s41467-025-56344-5 primary_locator: Figure 6i-j; Results: Inhibition of APT2 suppresses ferroptosis. organism: Human experimental_model: Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs exposure: HA-tagged rescue constructs; Figure 6j: 48-hour RSL3 challenge, n=3 independent experiments. Exact RSL3 concentrations follow the figure dose response and are not inferred here. limitations: C2S affects APT2 palmitoylation/localization and is not identical to the S122A catalytic-site perturbation. Null comparisons do not prove equivalence. No sulforaphane or solasonine tested in this rescue experiment.
Complete structured claim and evidence
S122A APT2 re-expression did not reproduce the wild-type reduction in GPX4 protein in APT2-depleted A375 cells.
Human A375 APT2 knockdown with HA-APT2 S122A re-expression → GPX4 protein abundance in human cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs
exposure
HA-tagged rescue constructs; Figure 6j: 48-hour RSL3 challenge, n=3 independent experiments. Exact RSL3 concentrations follow the figure dose response and are not inferred here.
limitations
C2S affects APT2 palmitoylation/localization and is not identical to the S122A catalytic-site perturbation. Null comparisons do not prove equivalence. No sulforaphane or solasonine tested in this rescue experiment.
organism
Human
primary_locator
Figure 6i-j; Results: Inhibition of APT2 suppresses ferroptosis.
primary_references
https://doi.org/10.1038/s41467-025-56344-5
trigger_kind
machinery_impairment Imported condition classification; unverified.
APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 42–48
Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs · source_derived_draft · unverified_draft
S122A APT2 re-expression did not reproduce the wild-type reduction in GPX4 protein in APT2-depleted A375 cells. primary_references: https://doi.org/10.1038/s41467-025-56344-5 primary_locator: Figure 6i-j; Results: Inhibition of APT2 suppresses ferroptosis. organism: Human experimental_model: Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs exposure: HA-tagged rescue constructs; Figure 6j: 48-hour RSL3 challenge, n=3 independent experiments. Exact RSL3 concentrations follow the figure dose response and are not inferred here. limitations: C2S affects APT2 palmitoylation/localization and is not identical to the S122A catalytic-site perturbation. Null comparisons do not prove equivalence. No sulforaphane or solasonine tested in this rescue experiment.
Complete structured claim and evidence
S122A APT2 re-expression did not reproduce wild-type restoration of RSL3 susceptibility in APT2-depleted A375 cells.
Human A375 APT2 knockdown with HA-APT2 S122A re-expression → RSL3-induced cell death in A375 cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs
exposure
HA-tagged rescue constructs; Figure 6j: 48-hour RSL3 challenge, n=3 independent experiments. Exact RSL3 concentrations follow the figure dose response and are not inferred here.
limitations
C2S affects APT2 palmitoylation/localization and is not identical to the S122A catalytic-site perturbation. Null comparisons do not prove equivalence. No sulforaphane or solasonine tested in this rescue experiment.
organism
Human
primary_locator
Figure 6i-j; Results: Inhibition of APT2 suppresses ferroptosis.
primary_references
https://doi.org/10.1038/s41467-025-56344-5
trigger_kind
machinery_impairment Imported condition classification; unverified.
APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 51–57
Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs · source_derived_draft · unverified_draft
S122A APT2 re-expression did not reproduce wild-type restoration of RSL3 susceptibility in APT2-depleted A375 cells. primary_references: https://doi.org/10.1038/s41467-025-56344-5 primary_locator: Figure 6i-j; Results: Inhibition of APT2 suppresses ferroptosis. organism: Human experimental_model: Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs exposure: HA-tagged rescue constructs; Figure 6j: 48-hour RSL3 challenge, n=3 independent experiments. Exact RSL3 concentrations follow the figure dose response and are not inferred here. limitations: C2S affects APT2 palmitoylation/localization and is not identical to the S122A catalytic-site perturbation. Null comparisons do not prove equivalence. No sulforaphane or solasonine tested in this rescue experiment.
Complete structured claim and evidence
Surface plasmon resonance reported solasonine binding to recombinant APT2, KD 2.982 micromolar.
Solasonine → LYPLA2 source_derived_draftungraded
Experimental context and source evidence
experimental_model
Recombinant human APT2 SPR; supporting cellular CETSA in NOZ/GBC-SD
exposure
SPR binding concentration series; cellular CETSA used 25 micromolar solasonine. Binding does not specify catalytic inhibition.
limitations
Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.
organism
Human
primary_locator
Figure 5J and Methods 2.20; CETSA Figure 5F-G.
primary_references
https://doi.org/10.1002/ptr.70245
APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 60–66
Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Recombinant human APT2 SPR; supporting cellular CETSA in NOZ/GBC-SD · source_derived_draft · unverified_draft
Surface plasmon resonance reported solasonine binding to recombinant APT2, KD 2.982 micromolar. primary_references: https://doi.org/10.1002/ptr.70245 primary_locator: Figure 5J and Methods 2.20; CETSA Figure 5F-G. organism: Human experimental_model: Recombinant human APT2 SPR; supporting cellular CETSA in NOZ/GBC-SD exposure: SPR binding concentration series; cellular CETSA used 25 micromolar solasonine. Binding does not specify catalytic inhibition. limitations: Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.
Complete structured claim and evidence
Solasonine increased STAT3 acyl-biotin-exchange signal.
Solasonine → STAT3 palmitoylation in human cells source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human NOZ and GBC-SD gallbladder cancer cells
exposure
Methods 2.2 describes 48-hour cellular drug treatments with refresh at 24 hours; exact concentration must be checked per figure and is not inferred from another assay.
limitations
Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.
organism
Human
primary_locator
Figure 5A; Supplementary Figure S4A; Results 3.5.
primary_references
https://doi.org/10.1002/ptr.70245
APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 69–75
Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Human NOZ and GBC-SD gallbladder cancer cells · source_derived_draft · unverified_draft
Solasonine increased STAT3 acyl-biotin-exchange signal. primary_references: https://doi.org/10.1002/ptr.70245 primary_locator: Figure 5A; Supplementary Figure S4A; Results 3.5. organism: Human experimental_model: Human NOZ and GBC-SD gallbladder cancer cells exposure: Methods 2.2 describes 48-hour cellular drug treatments with refresh at 24 hours; exact concentration must be checked per figure and is not inferred from another assay. limitations: Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.
Complete structured claim and evidence
Solasonine reduced nuclear phosphorylated STAT3, with cytoplasmic accumulation.
Solasonine → Nuclear phosphorylated STAT3 abundance in human cells source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human NOZ and GBC-SD gallbladder cancer cells
exposure
Methods 2.2 describes 48-hour cellular drug treatments with refresh at 24 hours; exact concentration must be checked per figure and is not inferred from another assay.
limitations
Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.
organism
Human
primary_locator
Figure 4B-D; Results 3.4.
primary_references
https://doi.org/10.1002/ptr.70245
APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 78–84
Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Human NOZ and GBC-SD gallbladder cancer cells · source_derived_draft · unverified_draft
Solasonine reduced nuclear phosphorylated STAT3, with cytoplasmic accumulation. primary_references: https://doi.org/10.1002/ptr.70245 primary_locator: Figure 4B-D; Results 3.4. organism: Human experimental_model: Human NOZ and GBC-SD gallbladder cancer cells exposure: Methods 2.2 describes 48-hour cellular drug treatments with refresh at 24 hours; exact concentration must be checked per figure and is not inferred from another assay. limitations: Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.
Complete structured claim and evidence
Solasonine did not change whole-cell phosphorylated STAT3 in the reported immunoblots.
Solasonine → Whole-cell phosphorylated STAT3 abundance in human cells source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human NOZ and GBC-SD gallbladder cancer cells
exposure
Methods 2.2 describes 48-hour cellular drug treatments with refresh at 24 hours; exact concentration must be checked per figure and is not inferred from another assay.
limitations
Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.
organism
Human
primary_locator
Figure 4A; Results 3.4.
primary_references
https://doi.org/10.1002/ptr.70245
APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 87–93
Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Human NOZ and GBC-SD gallbladder cancer cells · source_derived_draft · unverified_draft
Solasonine did not change whole-cell phosphorylated STAT3 in the reported immunoblots. primary_references: https://doi.org/10.1002/ptr.70245 primary_locator: Figure 4A; Results 3.4. organism: Human experimental_model: Human NOZ and GBC-SD gallbladder cancer cells exposure: Methods 2.2 describes 48-hour cellular drug treatments with refresh at 24 hours; exact concentration must be checked per figure and is not inferred from another assay. limitations: Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.
Complete structured claim and evidence
Solasonine did not change APT2 protein expression in the reported immunoblots.
Solasonine → APT2 protein abundance in human cells source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human NOZ and GBC-SD gallbladder cancer cells
exposure
Methods 2.2 describes 48-hour cellular drug treatments with refresh at 24 hours; exact concentration must be checked per figure and is not inferred from another assay.
limitations
Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.
organism
Human
primary_locator
Figure 5B; Supplementary Figure S4B; Results 3.5.
primary_references
https://doi.org/10.1002/ptr.70245
APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 96–102
Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Human NOZ and GBC-SD gallbladder cancer cells · source_derived_draft · unverified_draft
Solasonine did not change APT2 protein expression in the reported immunoblots. primary_references: https://doi.org/10.1002/ptr.70245 primary_locator: Figure 5B; Supplementary Figure S4B; Results 3.5. organism: Human experimental_model: Human NOZ and GBC-SD gallbladder cancer cells exposure: Methods 2.2 describes 48-hour cellular drug treatments with refresh at 24 hours; exact concentration must be checked per figure and is not inferred from another assay. limitations: Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.
Complete structured claim and evidence
The study reports a reduced LYPLA2 ELISA signal as reduced APT2 activity; the described assay does not establish catalytic turnover.
Solasonine → LYPLA2 antibody ELISA signal in human cell supernatants source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human NOZ and GBC-SD gallbladder cancer cells
exposure
Cell-supernatant ELISA; 0-50 ng/mL standards, anti-LYPLA2 plates, LYPLA2-HRP conjugate, H2O2/TMB chromogen, 450 nm readout with 630 nm reference. Cellular drug duration described as 48 hours.
limitations
Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.
organism
Human
primary_locator
Figure 5C versus Methods 2.17 ELISA Assay.
primary_references
https://doi.org/10.1002/ptr.70245
APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 105–111
Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Human NOZ and GBC-SD gallbladder cancer cells · source_derived_draft · unverified_draft
The study reports a reduced LYPLA2 ELISA signal as reduced APT2 activity; the described assay does not establish catalytic turnover. primary_references: https://doi.org/10.1002/ptr.70245 primary_locator: Figure 5C versus Methods 2.17 ELISA Assay. organism: Human experimental_model: Human NOZ and GBC-SD gallbladder cancer cells exposure: Cell-supernatant ELISA; 0-50 ng/mL standards, anti-LYPLA2 plates, LYPLA2-HRP conjugate, H2O2/TMB chromogen, 450 nm readout with 630 nm reference. Cellular drug duration described as 48 hours. limitations: Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.
Complete structured claim and evidence
Solasonine reduced APT2-STAT3 co-immunoprecipitation.
Solasonine → APT2-STAT3 co-immunoprecipitation in human cells source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human NOZ and GBC-SD gallbladder cancer cells
exposure
25 micromolar solasonine; main methods specify 48-hour cellular drug exposure.
limitations
Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.
organism
Human
primary_locator
Figure 5D-E; Results 3.5.
primary_references
https://doi.org/10.1002/ptr.70245
APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 114–120
Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Human NOZ and GBC-SD gallbladder cancer cells · source_derived_draft · unverified_draft
Solasonine reduced APT2-STAT3 co-immunoprecipitation. primary_references: https://doi.org/10.1002/ptr.70245 primary_locator: Figure 5D-E; Results 3.5. organism: Human experimental_model: Human NOZ and GBC-SD gallbladder cancer cells exposure: 25 micromolar solasonine; main methods specify 48-hour cellular drug exposure. limitations: Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.
Complete structured claim and evidence
Solasonine suppressed STAT3-driven GPX4 wild-type promoter reporter activity; binding-motif mutations abolished the reported responses.
Solasonine → GPX4 promoter luciferase activity in human cells source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human NOZ and GBC-SD gallbladder cancer cells
exposure
Methods 2.2 describes 48-hour cellular drug treatments with refresh at 24 hours; exact concentration must be checked per figure and is not inferred from another assay.
limitations
Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.
organism
Human
primary_locator
Figure 3I; Results 3.3; ChIP evidence in Figure 3E-H.
primary_references
https://doi.org/10.1002/ptr.70245
APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 123–129
Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Human NOZ and GBC-SD gallbladder cancer cells · source_derived_draft · unverified_draft
Solasonine suppressed STAT3-driven GPX4 wild-type promoter reporter activity; binding-motif mutations abolished the reported responses. primary_references: https://doi.org/10.1002/ptr.70245 primary_locator: Figure 3I; Results 3.3; ChIP evidence in Figure 3E-H. organism: Human experimental_model: Human NOZ and GBC-SD gallbladder cancer cells exposure: Methods 2.2 describes 48-hour cellular drug treatments with refresh at 24 hours; exact concentration must be checked per figure and is not inferred from another assay. limitations: Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.
Complete structured claim and evidence
Solasonine suppressed STAT3-driven SLC7A11 wild-type promoter reporter activity; binding-motif mutations abolished the reported responses.
Solasonine → SLC7A11 promoter luciferase activity in human cells source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human NOZ and GBC-SD gallbladder cancer cells
exposure
Methods 2.2 describes 48-hour cellular drug treatments with refresh at 24 hours; exact concentration must be checked per figure and is not inferred from another assay.
limitations
Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.
organism
Human
primary_locator
Figure 3I; Results 3.3; ChIP evidence in Figure 3E-H.
primary_references
https://doi.org/10.1002/ptr.70245
APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 132–138
Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Human NOZ and GBC-SD gallbladder cancer cells · source_derived_draft · unverified_draft
Solasonine suppressed STAT3-driven SLC7A11 wild-type promoter reporter activity; binding-motif mutations abolished the reported responses. primary_references: https://doi.org/10.1002/ptr.70245 primary_locator: Figure 3I; Results 3.3; ChIP evidence in Figure 3E-H. organism: Human experimental_model: Human NOZ and GBC-SD gallbladder cancer cells exposure: Methods 2.2 describes 48-hour cellular drug treatments with refresh at 24 hours; exact concentration must be checked per figure and is not inferred from another assay. limitations: Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.
Complete structured claim and evidence
STAT3 siRNA reduced GPX4 mRNA in the reported gallbladder cancer-cell experiments.
STAT3 siRNA knockdown in human gallbladder cancer cells → GPX4 mRNA abundance in human cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Human NOZ and GBC-SD gallbladder cancer cells
exposure
siSTAT3 versus control; reciprocal STAT3 overexpression increased mRNA/protein in the same reported figure group. Transfection duration not independently resolved here.
limitations
Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.
organism
Human
primary_locator
Figure 3A-D and Supplementary Figure S3A-B; Results 3.3.
primary_references
https://doi.org/10.1002/ptr.70245
trigger_kind
machinery_impairment Imported condition classification; unverified.
APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 141–147
Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Human NOZ and GBC-SD gallbladder cancer cells · source_derived_draft · unverified_draft
STAT3 siRNA reduced GPX4 mRNA in the reported gallbladder cancer-cell experiments. primary_references: https://doi.org/10.1002/ptr.70245 primary_locator: Figure 3A-D and Supplementary Figure S3A-B; Results 3.3. organism: Human experimental_model: Human NOZ and GBC-SD gallbladder cancer cells exposure: siSTAT3 versus control; reciprocal STAT3 overexpression increased mRNA/protein in the same reported figure group. Transfection duration not independently resolved here. limitations: Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.
Complete structured claim and evidence
STAT3 siRNA reduced SLC7A11 mRNA in the reported gallbladder cancer-cell experiments.
STAT3 siRNA knockdown in human gallbladder cancer cells → SLC7A11 mRNA abundance in human cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Human NOZ and GBC-SD gallbladder cancer cells
exposure
siSTAT3 versus control; reciprocal STAT3 overexpression increased mRNA/protein in the same reported figure group. Transfection duration not independently resolved here.
limitations
Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.
organism
Human
primary_locator
Figure 3A-D and Supplementary Figure S3A-B; Results 3.3.
primary_references
https://doi.org/10.1002/ptr.70245
trigger_kind
machinery_impairment Imported condition classification; unverified.
APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 150–156
Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Human NOZ and GBC-SD gallbladder cancer cells · source_derived_draft · unverified_draft
STAT3 siRNA reduced SLC7A11 mRNA in the reported gallbladder cancer-cell experiments. primary_references: https://doi.org/10.1002/ptr.70245 primary_locator: Figure 3A-D and Supplementary Figure S3A-B; Results 3.3. organism: Human experimental_model: Human NOZ and GBC-SD gallbladder cancer cells exposure: siSTAT3 versus control; reciprocal STAT3 overexpression increased mRNA/protein in the same reported figure group. Transfection duration not independently resolved here. limitations: Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.
Complete structured claim and evidence
Solasonine did not increase STAT3 palmitoylation in the reported APT2-D13A/L11A mutant setting.
APT2-D13A/L11A expression with solasonine in human gallbladder cancer cells → STAT3 palmitoylation in human cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Human NOZ and GBC-SD gallbladder cancer cells
exposure
Methods 2.2 describes 48-hour cellular drug treatments with refresh at 24 hours; exact concentration must be checked per figure and is not inferred from another assay.
limitations
Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.
organism
Human
primary_locator
Figure 6E; Supplementary Figure S5A; Results 3.6.
primary_references
https://doi.org/10.1002/ptr.70245
trigger_kind
machinery_impairment Imported condition classification; unverified.
APT2, STAT3 and GPX4: opposing branches and assay qualification · lines 159–165
Primary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · supports · Human NOZ and GBC-SD gallbladder cancer cells · source_derived_draft · unverified_draft
Solasonine did not increase STAT3 palmitoylation in the reported APT2-D13A/L11A mutant setting. primary_references: https://doi.org/10.1002/ptr.70245 primary_locator: Figure 6E; Supplementary Figure S5A; Results 3.6. organism: Human experimental_model: Human NOZ and GBC-SD gallbladder cancer cells exposure: Methods 2.2 describes 48-hour cellular drug treatments with refresh at 24 hours; exact concentration must be checked per figure and is not inferred from another assay. limitations: Human cancer-cell experiments; no clinical or dietary inference. Solasonine exposure is not equivalent to APT2 depletion, ML349, or sulforaphane. Mutant rescue does not by itself establish selectivity or normal baseline mutant function. Figure 5C calls this APT2 activity, but Methods 2.17 describes an anti-LYPLA2 ELISA with mass-concentration standards and an HRP/TMB readout from cell supernatants. No direct APT2 substrate-turnover assay is described there. The result is retained as an author-labelled activity proxy, not established catalytic inhibition. This methodological qualification does not invalidate the separately reported binding or cellular observations.
Complete structured claim and evidence
ML349 increased STAT3 palmitoylation in the reported reconstituted HEK293T experiment.
ML349, experimental APT2 inhibitor → STAT3 palmitoylation in human cells source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human HEK293T; DHHC7 knockout reconstituted with HA-DHHC7 and Flag-STAT3; DHHC construct species is not established as human for this figure.
exposure
20 micromolar ML349 for 36 hours before Alk14 labeling; labeling methods specify 50 micromolar Alk14 for 5 hours.
limitations
Reported cellular result, not a GPX4 time-course experiment. Overexpressed DHHC constructs in much of the study are mouse proteins; human constructs are explicitly identified only where confirmed. APT2 depletion, selective inhibitor exposure and sulforaphane are different interventions.
organism
Human
primary_locator
Figure 2f; Extended Data 7d; APT2 depalmitoylates p-STAT3.
primary_references
https://doi.org/10.1038/s41586-020-2799-2
APT2-STAT3 cycling and a competing sulforaphane target route · lines 6–12
Selected primary observations: 10.1038/s41586-020-2799-2 and 10.1038/s41388-020-1335-z. · supports · Human HEK293T; DHHC7 knockout reconstituted with HA-DHHC7 and Flag-STAT3; DHHC construct species is not established as human for this figure. · source_derived_draft · unverified_draft
ML349 increased STAT3 palmitoylation in the reported reconstituted HEK293T experiment. primary_references: https://doi.org/10.1038/s41586-020-2799-2 primary_locator: Figure 2f; Extended Data 7d; APT2 depalmitoylates p-STAT3. organism: Human experimental_model: Human HEK293T; DHHC7 knockout reconstituted with HA-DHHC7 and Flag-STAT3; DHHC construct species is not established as human for this figure. exposure: 20 micromolar ML349 for 36 hours before Alk14 labeling; labeling methods specify 50 micromolar Alk14 for 5 hours. limitations: Reported cellular result, not a GPX4 time-course experiment. Overexpressed DHHC constructs in much of the study are mouse proteins; human constructs are explicitly identified only where confirmed. APT2 depletion, selective inhibitor exposure and sulforaphane are different interventions.
Complete structured claim and evidence
LYPLA2 siRNA increased STAT3 palmitoylation in the reported reconstituted HEK293T experiment.
Human APT2/LYPLA2 knockdown in HEK293T → STAT3 palmitoylation in human cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Human HEK293T; DHHC7 knockout reconstituted with HA-DHHC7 and Flag-STAT3; DHHC construct species is not established as human for this figure.
exposure
LYPLA2 siRNA before Alk14 labeling; Figure 2f states 36 hours before labeling; exact siRNA amount unresolved.
limitations
Reported cellular result, not a GPX4 time-course experiment. Overexpressed DHHC constructs in much of the study are mouse proteins; human constructs are explicitly identified only where confirmed. APT2 depletion, selective inhibitor exposure and sulforaphane are different interventions.
organism
Human
primary_locator
Figure 2f; Extended Data 7d.
primary_references
https://doi.org/10.1038/s41586-020-2799-2
trigger_kind
machinery_impairment Imported condition classification; unverified.
APT2-STAT3 cycling and a competing sulforaphane target route · lines 15–21
Selected primary observations: 10.1038/s41586-020-2799-2 and 10.1038/s41388-020-1335-z. · supports · Human HEK293T; DHHC7 knockout reconstituted with HA-DHHC7 and Flag-STAT3; DHHC construct species is not established as human for this figure. · source_derived_draft · unverified_draft
LYPLA2 siRNA increased STAT3 palmitoylation in the reported reconstituted HEK293T experiment. primary_references: https://doi.org/10.1038/s41586-020-2799-2 primary_locator: Figure 2f; Extended Data 7d. organism: Human experimental_model: Human HEK293T; DHHC7 knockout reconstituted with HA-DHHC7 and Flag-STAT3; DHHC construct species is not established as human for this figure. exposure: LYPLA2 siRNA before Alk14 labeling; Figure 2f states 36 hours before labeling; exact siRNA amount unresolved. limitations: Reported cellular result, not a GPX4 time-course experiment. Overexpressed DHHC constructs in much of the study are mouse proteins; human constructs are explicitly identified only where confirmed. APT2 depletion, selective inhibitor exposure and sulforaphane are different interventions.
Complete structured claim and evidence
APT2 knockdown reduced nuclear p-STAT3 in the HEK293T fractionation experiment.
Human APT2/LYPLA2 knockdown in HEK293T → Nuclear phosphorylated STAT3 abundance in human cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Human HEK293T subcellular fractionation
exposure
LYPLA2 siRNA; exact dose/duration for this panel unresolved.
limitations
Reported cellular result, not a GPX4 time-course experiment. Overexpressed DHHC constructs in much of the study are mouse proteins; human constructs are explicitly identified only where confirmed. APT2 depletion, selective inhibitor exposure and sulforaphane are different interventions.
organism
Human
primary_locator
Figure 2g; APT2 depalmitoylates p-STAT3.
primary_references
https://doi.org/10.1038/s41586-020-2799-2
trigger_kind
machinery_impairment Imported condition classification; unverified.
APT2-STAT3 cycling and a competing sulforaphane target route · lines 24–30
Selected primary observations: 10.1038/s41586-020-2799-2 and 10.1038/s41388-020-1335-z. · supports · Human HEK293T subcellular fractionation · source_derived_draft · unverified_draft
APT2 knockdown reduced nuclear p-STAT3 in the HEK293T fractionation experiment. primary_references: https://doi.org/10.1038/s41586-020-2799-2 primary_locator: Figure 2g; APT2 depalmitoylates p-STAT3. organism: Human experimental_model: Human HEK293T subcellular fractionation exposure: LYPLA2 siRNA; exact dose/duration for this panel unresolved. limitations: Reported cellular result, not a GPX4 time-course experiment. Overexpressed DHHC constructs in much of the study are mouse proteins; human constructs are explicitly identified only where confirmed. APT2 depletion, selective inhibitor exposure and sulforaphane are different interventions.
Complete structured claim and evidence
APT2 knockdown reduced STAT3 transcriptional activity in the reported HEK293T experiments.
Human APT2/LYPLA2 knockdown in HEK293T → STAT3-dependent transcriptional output in human cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
experimental_model
Human HEK293T
exposure
LYPLA2 siRNA; exact exposure unresolved.
limitations
Reported cellular result, not a GPX4 time-course experiment. Overexpressed DHHC constructs in much of the study are mouse proteins; human constructs are explicitly identified only where confirmed. APT2 depletion, selective inhibitor exposure and sulforaphane are different interventions.
organism
Human
primary_locator
Extended Data 7e-f and Results: APT2 depalmitoylates p-STAT3.
primary_references
https://doi.org/10.1038/s41586-020-2799-2
trigger_kind
machinery_impairment Imported condition classification; unverified.
APT2-STAT3 cycling and a competing sulforaphane target route · lines 33–39
Selected primary observations: 10.1038/s41586-020-2799-2 and 10.1038/s41388-020-1335-z. · supports · Human HEK293T · source_derived_draft · unverified_draft
APT2 knockdown reduced STAT3 transcriptional activity in the reported HEK293T experiments. primary_references: https://doi.org/10.1038/s41586-020-2799-2 primary_locator: Extended Data 7e-f and Results: APT2 depalmitoylates p-STAT3. organism: Human experimental_model: Human HEK293T exposure: LYPLA2 siRNA; exact exposure unresolved. limitations: Reported cellular result, not a GPX4 time-course experiment. Overexpressed DHHC constructs in much of the study are mouse proteins; human constructs are explicitly identified only where confirmed. APT2 depletion, selective inhibitor exposure and sulforaphane are different interventions.
Complete structured claim and evidence
Wild-type APT2 expression reduced STAT3 palmitoylation.
Human APT2 WT expression in HEK293T → STAT3 palmitoylation in human cells source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human HEK293T with expressed APT2 and Flag-STAT3
exposure
Expression constructs; 50 micromolar Alk14 labeling for 5 hours; expression duration unresolved.
limitations
C2S disrupts the APT2 palmitoylation site; S122A alters its catalytic site. They are not interchangeable controls. Null results do not establish equivalence. GPX4 was not an endpoint.
organism
Human
primary_locator
Figure 2d; Extended Data 7b-c.
primary_references
https://doi.org/10.1038/s41586-020-2799-2
APT2-STAT3 cycling and a competing sulforaphane target route · lines 42–48
Selected primary observations: 10.1038/s41586-020-2799-2 and 10.1038/s41388-020-1335-z. · supports · Human HEK293T with expressed APT2 and Flag-STAT3 · source_derived_draft · unverified_draft
Wild-type APT2 expression reduced STAT3 palmitoylation. primary_references: https://doi.org/10.1038/s41586-020-2799-2 primary_locator: Figure 2d; Extended Data 7b-c. organism: Human experimental_model: Human HEK293T with expressed APT2 and Flag-STAT3 exposure: Expression constructs; 50 micromolar Alk14 labeling for 5 hours; expression duration unresolved. limitations: C2S disrupts the APT2 palmitoylation site; S122A alters its catalytic site. They are not interchangeable controls. Null results do not establish equivalence. GPX4 was not an endpoint.
Complete structured claim and evidence
APT2-C2S expression did not reproduce the wild-type reduction in STAT3 palmitoylation.
Human APT2 C2S expression in HEK293T → STAT3 palmitoylation in human cells source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human HEK293T with expressed APT2 and Flag-STAT3
exposure
Expression constructs; 50 micromolar Alk14 labeling for 5 hours; expression duration unresolved.
limitations
C2S disrupts the APT2 palmitoylation site; S122A alters its catalytic site. They are not interchangeable controls. Null results do not establish equivalence. GPX4 was not an endpoint.
organism
Human
primary_locator
Figure 2d; Extended Data 7b-c.
primary_references
https://doi.org/10.1038/s41586-020-2799-2
APT2-STAT3 cycling and a competing sulforaphane target route · lines 51–57
Selected primary observations: 10.1038/s41586-020-2799-2 and 10.1038/s41388-020-1335-z. · supports · Human HEK293T with expressed APT2 and Flag-STAT3 · source_derived_draft · unverified_draft
APT2-C2S expression did not reproduce the wild-type reduction in STAT3 palmitoylation. primary_references: https://doi.org/10.1038/s41586-020-2799-2 primary_locator: Figure 2d; Extended Data 7b-c. organism: Human experimental_model: Human HEK293T with expressed APT2 and Flag-STAT3 exposure: Expression constructs; 50 micromolar Alk14 labeling for 5 hours; expression duration unresolved. limitations: C2S disrupts the APT2 palmitoylation site; S122A alters its catalytic site. They are not interchangeable controls. Null results do not establish equivalence. GPX4 was not an endpoint.
Complete structured claim and evidence
APT2-S122A expression did not reproduce the wild-type reduction in STAT3 palmitoylation.
Human APT2 S122A expression in HEK293T → STAT3 palmitoylation in human cells source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human HEK293T with expressed APT2 and Flag-STAT3
exposure
Expression constructs; 50 micromolar Alk14 labeling for 5 hours; expression duration unresolved.
limitations
C2S disrupts the APT2 palmitoylation site; S122A alters its catalytic site. They are not interchangeable controls. Null results do not establish equivalence. GPX4 was not an endpoint.
organism
Human
primary_locator
Figure 2d; Extended Data 7b-c.
primary_references
https://doi.org/10.1038/s41586-020-2799-2
APT2-STAT3 cycling and a competing sulforaphane target route · lines 60–66
Selected primary observations: 10.1038/s41586-020-2799-2 and 10.1038/s41388-020-1335-z. · supports · Human HEK293T with expressed APT2 and Flag-STAT3 · source_derived_draft · unverified_draft
APT2-S122A expression did not reproduce the wild-type reduction in STAT3 palmitoylation. primary_references: https://doi.org/10.1038/s41586-020-2799-2 primary_locator: Figure 2d; Extended Data 7b-c. organism: Human experimental_model: Human HEK293T with expressed APT2 and Flag-STAT3 exposure: Expression constructs; 50 micromolar Alk14 labeling for 5 hours; expression duration unresolved. limitations: C2S disrupts the APT2 palmitoylation site; S122A alters its catalytic site. They are not interchangeable controls. Null results do not establish equivalence. GPX4 was not an endpoint.
Complete structured claim and evidence
Human ZDHHC7 expression increased STAT3 palmitoylation in the human-construct confirmation experiment.
Human ZDHHC7 expression in HEK293T → STAT3 palmitoylation in human cells source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human HEK293T expressing human DHHC proteins
exposure
Comparison of Flag-tagged human DHHC3, DHHC7 and DHHC19 with HA-STAT3; Alk14 assay.
limitations
Human-construct confirmation is separate from the mouse-DHHC screening experiments. Selected result/legend reviewed; raw gel intensities not reanalyzed.
organism
Human
primary_locator
Extended Data Figure 2f; Results: STAT3 is palmitoylated by DHHC7.
primary_references
https://doi.org/10.1038/s41586-020-2799-2
APT2-STAT3 cycling and a competing sulforaphane target route · lines 69–75
Selected primary observations: 10.1038/s41586-020-2799-2 and 10.1038/s41388-020-1335-z. · supports · Human HEK293T expressing human DHHC proteins · source_derived_draft · unverified_draft
Human ZDHHC7 expression increased STAT3 palmitoylation in the human-construct confirmation experiment. primary_references: https://doi.org/10.1038/s41586-020-2799-2 primary_locator: Extended Data Figure 2f; Results: STAT3 is palmitoylated by DHHC7. organism: Human experimental_model: Human HEK293T expressing human DHHC proteins exposure: Comparison of Flag-tagged human DHHC3, DHHC7 and DHHC19 with HA-STAT3; Alk14 assay. limitations: Human-construct confirmation is separate from the mouse-DHHC screening experiments. Selected result/legend reviewed; raw gel intensities not reanalyzed.
Complete structured claim and evidence
The sulforaphane-derived activity-based probe captured STAT3 from HBCX34 cells.
Sulforaphane-derived activity-based probe → STAT3 source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human HBCx34 breast cancer patient-derived xenograft tumor cells
exposure
5 micromolar SFN-ABP for 30 minutes at 37 C in serum-free DMEM; click chemistry and avidin enrichment followed by anti-STAT3 immunoblot.
limitations
The chemical probe and stabilized formulation are separate experimental actors. Capture supports engagement but does not identify the modified STAT3 cysteine or demonstrate that APT2 mediates the effect. No GPX4 time-course endpoint. Primary cell/PDX studies are not evidence of benefit from dietary broccoli.
organism
Human
primary_locator
Figure 4c; Supplementary Methods: Affinity pull-down assays.
primary_references
https://doi.org/10.1038/s41388-020-1335-z
APT2-STAT3 cycling and a competing sulforaphane target route · lines 78–84
Selected primary observations: 10.1038/s41586-020-2799-2 and 10.1038/s41388-020-1335-z. · supports · Human HBCx34 breast cancer patient-derived xenograft tumor cells · source_derived_draft · unverified_draft
The sulforaphane-derived activity-based probe captured STAT3 from HBCX34 cells. primary_references: https://doi.org/10.1038/s41388-020-1335-z primary_locator: Figure 4c; Supplementary Methods: Affinity pull-down assays. organism: Human experimental_model: Human HBCx34 breast cancer patient-derived xenograft tumor cells exposure: 5 micromolar SFN-ABP for 30 minutes at 37 C in serum-free DMEM; click chemistry and avidin enrichment followed by anti-STAT3 immunoblot. limitations: The chemical probe and stabilized formulation are separate experimental actors. Capture supports engagement but does not identify the modified STAT3 cysteine or demonstrate that APT2 mediates the effect. No GPX4 time-course endpoint. Primary cell/PDX studies are not evidence of benefit from dietary broccoli.
Complete structured claim and evidence
The sulforaphane-derived activity-based probe captured STAT3 from BB3RC61 cells.
Sulforaphane-derived activity-based probe → STAT3 source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human antiestrogen-resistant metastatic breast cancer sample BB3RC61
exposure
5 micromolar SFN-ABP for 30 minutes at 37 C in serum-free DMEM; click chemistry and avidin enrichment followed by anti-STAT3 immunoblot.
limitations
The chemical probe and stabilized formulation are separate experimental actors. Capture supports engagement but does not identify the modified STAT3 cysteine or demonstrate that APT2 mediates the effect. No GPX4 time-course endpoint. Primary cell/PDX studies are not evidence of benefit from dietary broccoli.
organism
Human
primary_locator
Figure 4e; Supplementary Methods: Affinity pull-down assays.
primary_references
https://doi.org/10.1038/s41388-020-1335-z
APT2-STAT3 cycling and a competing sulforaphane target route · lines 87–93
Selected primary observations: 10.1038/s41586-020-2799-2 and 10.1038/s41388-020-1335-z. · supports · Human antiestrogen-resistant metastatic breast cancer sample BB3RC61 · source_derived_draft · unverified_draft
The sulforaphane-derived activity-based probe captured STAT3 from BB3RC61 cells. primary_references: https://doi.org/10.1038/s41388-020-1335-z primary_locator: Figure 4e; Supplementary Methods: Affinity pull-down assays. organism: Human experimental_model: Human antiestrogen-resistant metastatic breast cancer sample BB3RC61 exposure: 5 micromolar SFN-ABP for 30 minutes at 37 C in serum-free DMEM; click chemistry and avidin enrichment followed by anti-STAT3 immunoblot. limitations: The chemical probe and stabilized formulation are separate experimental actors. Capture supports engagement but does not identify the modified STAT3 cysteine or demonstrate that APT2 mediates the effect. No GPX4 time-course endpoint. Primary cell/PDX studies are not evidence of benefit from dietary broccoli.
Complete structured claim and evidence
SFX-01 reduced phosphorylated STAT3 relative to antiestrogen-only treatments in BB3RC61 cells.
SFX-01, sulforaphane stabilized in an alpha-cyclodextrin complex → Whole-cell phosphorylated STAT3 abundance in human cells source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human antiestrogen-resistant metastatic breast cancer sample BB3RC61
exposure
72-hour treatment. Supplementary reagent protocol uses 5 micromolar SFX-01, 1 micromolar 4-OH-tamoxifen or 0.1 micromolar fulvestrant; these concentrations are explicitly stated for cell lines, and patient-specific dosing is not independently confirmed here.
limitations
The chemical probe and stabilized formulation are separate experimental actors. Capture supports engagement but does not identify the modified STAT3 cysteine or demonstrate that APT2 mediates the effect. No GPX4 time-course endpoint. Primary cell/PDX studies are not evidence of benefit from dietary broccoli.
organism
Human
primary_locator
Figure 4d; Results: SFX-01 targets STAT3 signaling.
primary_references
https://doi.org/10.1038/s41388-020-1335-z
APT2-STAT3 cycling and a competing sulforaphane target route · lines 96–102
Selected primary observations: 10.1038/s41586-020-2799-2 and 10.1038/s41388-020-1335-z. · supports · Human antiestrogen-resistant metastatic breast cancer sample BB3RC61 · source_derived_draft · unverified_draft
SFX-01 reduced phosphorylated STAT3 relative to antiestrogen-only treatments in BB3RC61 cells. primary_references: https://doi.org/10.1038/s41388-020-1335-z primary_locator: Figure 4d; Results: SFX-01 targets STAT3 signaling. organism: Human experimental_model: Human antiestrogen-resistant metastatic breast cancer sample BB3RC61 exposure: 72-hour treatment. Supplementary reagent protocol uses 5 micromolar SFX-01, 1 micromolar 4-OH-tamoxifen or 0.1 micromolar fulvestrant; these concentrations are explicitly stated for cell lines, and patient-specific dosing is not independently confirmed here. limitations: The chemical probe and stabilized formulation are separate experimental actors. Capture supports engagement but does not identify the modified STAT3 cysteine or demonstrate that APT2 mediates the effect. No GPX4 time-course endpoint. Primary cell/PDX studies are not evidence of benefit from dietary broccoli.
Complete structured claim and evidence
SFX-01 did not repress STAT3 activity in the reported previously SFX-01-treated, resistant BB7121 sample.
SFX-01, sulforaphane stabilized in an alpha-cyclodextrin complex → Whole-cell phosphorylated STAT3 abundance in human cells source_derived_draftungraded
Experimental context and source evidence
experimental_model
Human metastatic breast cancer patient-derived sample BB7121
exposure
Prior clinical SFX-01 exposure with progression; ex vivo STAT3 assay. Exact panel exposure unresolved.
limitations
The chemical probe and stabilized formulation are separate experimental actors. Capture supports engagement but does not identify the modified STAT3 cysteine or demonstrate that APT2 mediates the effect. No GPX4 time-course endpoint. Primary cell/PDX studies are not evidence of benefit from dietary broccoli. A single resistant sample does not determine the mechanism of resistance. Supplementary legend/main-text result reviewed; raw image not quantitatively reanalyzed.
organism
Human
primary_locator
Results: SFX-01 targets STAT3 signaling; Supplementary Figure S4c.
primary_references
https://doi.org/10.1038/s41388-020-1335-z
APT2-STAT3 cycling and a competing sulforaphane target route · lines 105–111
Selected primary observations: 10.1038/s41586-020-2799-2 and 10.1038/s41388-020-1335-z. · supports · Human metastatic breast cancer patient-derived sample BB7121 · source_derived_draft · unverified_draft
SFX-01 did not repress STAT3 activity in the reported previously SFX-01-treated, resistant BB7121 sample. primary_references: https://doi.org/10.1038/s41388-020-1335-z primary_locator: Results: SFX-01 targets STAT3 signaling; Supplementary Figure S4c. organism: Human experimental_model: Human metastatic breast cancer patient-derived sample BB7121 exposure: Prior clinical SFX-01 exposure with progression; ex vivo STAT3 assay. Exact panel exposure unresolved. limitations: The chemical probe and stabilized formulation are separate experimental actors. Capture supports engagement but does not identify the modified STAT3 cysteine or demonstrate that APT2 mediates the effect. No GPX4 time-course endpoint. Primary cell/PDX studies are not evidence of benefit from dietary broccoli. A single resistant sample does not determine the mechanism of resistance. Supplementary legend/main-text result reviewed; raw image not quantitatively reanalyzed.
Complete structured claim and evidence

Availability and dependencies

Each situation shows the normal role first, then what the sources report under a specific condition. A shortfall in the diet, a fault in the machinery, and a low blood reading are kept separate because they are not the same thing.

When synthesis is experimentally blocked

Condition: machinery_impairment · BSO exposure in a biochemical inhibition model.

Normal role: GCL forms the first biosynthetic intermediate.

Recorded consequence: A phosphorylated inhibitory species blocks GCL.

Scope: Purified yeast GCL

The published human K562 dual-targeting screen reports SLC16A11/SLC25A39 genetic interaction pi=0.154314615559463 with significance value 0.0185030434905457 under Glc15. This is a relative-fitness interaction estimate, not restoration of mitochondrial glutathione.

Condition: machinery_impairment · 15-day growth screen; 25 mM glucose, 1 mM sodium pyruvate; 10% dialyzed FBS and 50 microgram/mL uridine.

Normal role: SLC25A39 supplies mitochondrial glutathione; this experiment measures paired genetic targeting and pooled relative fitness.

Recorded consequence: The published human K562 dual-targeting screen reports SLC16A11/SLC25A39 genetic interaction pi=0.154314615559463 with significance value 0.0185030434905457 under Glc15. This is a relative-fitness interaction estimate, not restoration of mitochondrial glutathione.

Scope: Human K562 pooled CRISPR screen; two batches; paired SaCas9/SpCas9 guides

Wild-type APT2 re-expression lowered GPX4 protein in APT2-depleted A375 cells.

Condition: machinery_impairment · HA-tagged rescue constructs; Figure 6j: 48-hour RSL3 challenge, n=3 independent experiments. Exact RSL3 concentrations follow the figure dose response and are not inferred here.

Normal role: GPX4 and the SLC7A11/GSH system participate in lipid peroxide defense; protein abundance alone is not enzyme flux.

Recorded consequence: Wild-type APT2 re-expression lowered GPX4 protein in APT2-depleted A375 cells.

Scope: Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs

LYPLA2 siRNA increased STAT3 palmitoylation in the reported reconstituted HEK293T experiment.

Condition: machinery_impairment · LYPLA2 siRNA before Alk14 labeling; Figure 2f states 36 hours before labeling; exact siRNA amount unresolved.

Normal role: STAT3 cycling is an upstream connection to antioxidant transcription in other recorded contexts; no glutathione loss is measured here.

Recorded consequence: LYPLA2 siRNA increased STAT3 palmitoylation in the reported reconstituted HEK293T experiment.

Scope: Human HEK293T; DHHC7 knockout reconstituted with HA-DHHC7 and Flag-STAT3; DHHC construct species is not established as human for this figure.

When the first synthesis enzyme is impaired

Condition: machinery_impairment · The four studied inherited GCLC variants.

Normal role: GCLC and GCLM support glutathione synthesis.

Recorded consequence: Mutant transfectants produced less GSH; modifier-subunit association changed activity.

Scope: Experimental expression of human variants

The published human K562 dual-targeting screen reports SLC16A11/SLC25A39 genetic interaction pi=0.0272123713337914 with significance value 0.578178616323455 under Gal15. This is a relative-fitness interaction estimate, not restoration of mitochondrial glutathione.

Condition: machinery_impairment · 15-day growth screen; 25 mM galactose replacing glucose, 1 mM sodium pyruvate; 10% dialyzed FBS and 50 microgram/mL uridine.

Normal role: SLC25A39 supplies mitochondrial glutathione; this experiment measures paired genetic targeting and pooled relative fitness.

Recorded consequence: The published human K562 dual-targeting screen reports SLC16A11/SLC25A39 genetic interaction pi=0.0272123713337914 with significance value 0.578178616323455 under Gal15. This is a relative-fitness interaction estimate, not restoration of mitochondrial glutathione.

Scope: Human K562 pooled CRISPR screen; two batches; paired SaCas9/SpCas9 guides

Wild-type APT2 re-expression restored RSL3 susceptibility in APT2-depleted A375 cells.

Normal role: GPX4 and the SLC7A11/GSH system participate in lipid peroxide defense; protein abundance alone is not enzyme flux.

Recorded consequence: Wild-type APT2 re-expression restored RSL3 susceptibility in APT2-depleted A375 cells.

Scope: Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs

APT2 knockdown reduced nuclear p-STAT3 in the HEK293T fractionation experiment.

Condition: machinery_impairment · LYPLA2 siRNA; exact dose/duration for this panel unresolved.

Normal role: STAT3 cycling is an upstream connection to antioxidant transcription in other recorded contexts; no glutathione loss is measured here.

Recorded consequence: APT2 knockdown reduced nuclear p-STAT3 in the HEK293T fractionation experiment.

Scope: Human HEK293T subcellular fractionation

When the second synthesis enzyme fails

Condition: machinery_impairment · Studied GSS loss-of-function variants.

Normal role: GSS adds glycine to gamma-glutamylcysteine.

Recorded consequence: GSH production is impaired and some genotypes are associated with 5-oxoprolinuria.

Scope: Human enzyme assays and inherited-disease tissues

The published human K562 dual-targeting screen reports SLC16A11/SLC25A39 genetic interaction pi=0.0805858670811976 with significance value 0.612290402312043 under Anti15. This is a relative-fitness interaction estimate, not restoration of mitochondrial glutathione.

Condition: machinery_impairment · 15-day growth screen; 25 mM glucose, 1 mM sodium pyruvate, 100 nM antimycin; 10% dialyzed FBS and 50 microgram/mL uridine.

Normal role: SLC25A39 supplies mitochondrial glutathione; this experiment measures paired genetic targeting and pooled relative fitness.

Recorded consequence: The published human K562 dual-targeting screen reports SLC16A11/SLC25A39 genetic interaction pi=0.0805858670811976 with significance value 0.612290402312043 under Anti15. This is a relative-fitness interaction estimate, not restoration of mitochondrial glutathione.

Scope: Human K562 pooled CRISPR screen; two batches; paired SaCas9/SpCas9 guides

C2S APT2 re-expression did not reproduce the wild-type reduction in GPX4 protein in APT2-depleted A375 cells.

Normal role: GPX4 and the SLC7A11/GSH system participate in lipid peroxide defense; protein abundance alone is not enzyme flux.

Recorded consequence: C2S APT2 re-expression did not reproduce the wild-type reduction in GPX4 protein in APT2-depleted A375 cells.

Scope: Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs

APT2 knockdown reduced STAT3 transcriptional activity in the reported HEK293T experiments.

Condition: machinery_impairment · LYPLA2 siRNA; exact exposure unresolved.

Normal role: STAT3 cycling is an upstream connection to antioxidant transcription in other recorded contexts; no glutathione loss is measured here.

Recorded consequence: APT2 knockdown reduced STAT3 transcriptional activity in the reported HEK293T experiments.

Scope: Human HEK293T

When glutathione cannot reach mitochondria

Condition: machinery_impairment · Experimental carrier loss.

Normal role: A39-dependent import supplies mitochondrial GSH.

Recorded consequence: Mitochondrial GSH falls despite preserved whole-cell GSH.

Scope: Mammalian cells

The published human K562 dual-targeting screen reports SLC16A11/SLC25A39 genetic interaction pi=0.155012680942449 with significance value 0.0621187730457448 under Pyr15. This is a relative-fitness interaction estimate, not restoration of mitochondrial glutathione.

Condition: machinery_impairment · 15-day growth screen; 25 mM glucose, without added sodium pyruvate; 10% dialyzed FBS and 50 microgram/mL uridine.

Normal role: SLC25A39 supplies mitochondrial glutathione; this experiment measures paired genetic targeting and pooled relative fitness.

Recorded consequence: The published human K562 dual-targeting screen reports SLC16A11/SLC25A39 genetic interaction pi=0.155012680942449 with significance value 0.0621187730457448 under Pyr15. This is a relative-fitness interaction estimate, not restoration of mitochondrial glutathione.

Scope: Human K562 pooled CRISPR screen; two batches; paired SaCas9/SpCas9 guides

C2S APT2 re-expression did not reproduce wild-type restoration of RSL3 susceptibility in APT2-depleted A375 cells.

Normal role: GPX4 and the SLC7A11/GSH system participate in lipid peroxide defense; protein abundance alone is not enzyme flux.

Recorded consequence: C2S APT2 re-expression did not reproduce wild-type restoration of RSL3 susceptibility in APT2-depleted A375 cells.

Scope: Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs

When glutathione salvage fails

Condition: machinery_impairment · Ggt1 deletion in mice.

Normal role: GGT makes extracellular glutathione usable as a cysteine source.

Recorded consequence: Extracellular GSH rises while several tissue stores and plasma cyst(e)ine fall.

Scope: Mouse genetic model

S122A APT2 re-expression did not reproduce the wild-type reduction in GPX4 protein in APT2-depleted A375 cells.

Normal role: GPX4 and the SLC7A11/GSH system participate in lipid peroxide defense; protein abundance alone is not enzyme flux.

Recorded consequence: S122A APT2 re-expression did not reproduce the wild-type reduction in GPX4 protein in APT2-depleted A375 cells.

Scope: Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs

When GSNO turnover is impaired

Condition: machinery_impairment · Mouse reductase-gene deletion.

Normal role: GSNOR controls cellular nitrosothiol abundance.

Recorded consequence: GSNO consumption is lost and cellular nitrosothiols rise.

Scope: Mouse genetic experiment

S122A APT2 re-expression did not reproduce wild-type restoration of RSL3 susceptibility in APT2-depleted A375 cells.

Normal role: GPX4 and the SLC7A11/GSH system participate in lipid peroxide defense; protein abundance alone is not enzyme flux.

Recorded consequence: S122A APT2 re-expression did not reproduce wild-type restoration of RSL3 susceptibility in APT2-depleted A375 cells.

Scope: Human A375 melanoma cells with APT2 shRNA and lentiviral rescue constructs

When a reactive drug metabolite inhibits synthesis

Condition: machinery_impairment · Experimental NAPQI exposure.

Normal role: GSS completes GSH synthesis.

Recorded consequence: Covalent enzyme modification irreversibly inhibits activity in vitro.

Scope: Purified-enzyme assay

STAT3 siRNA reduced GPX4 mRNA in the reported gallbladder cancer-cell experiments.

Condition: machinery_impairment · siSTAT3 versus control; reciprocal STAT3 overexpression increased mRNA/protein in the same reported figure group. Transfection duration not independently resolved here.

Normal role: GPX4 and the SLC7A11/GSH system participate in lipid peroxide defense; protein abundance alone is not enzyme flux.

Recorded consequence: STAT3 siRNA reduced GPX4 mRNA in the reported gallbladder cancer-cell experiments.

Scope: Human NOZ and GBC-SD gallbladder cancer cells

When measured precursor availability and GSH synthesis are low

Condition: nutrient_deficiency · Low measured erythrocyte precursors in this older cohort.

Normal role: Glycine and cysteine supply GSH synthesis.

Recorded consequence: GSH synthesis and concentration were lower; supplementation increased both.

Scope: Small human tracer study

STAT3 siRNA reduced SLC7A11 mRNA in the reported gallbladder cancer-cell experiments.

Normal role: GPX4 and the SLC7A11/GSH system participate in lipid peroxide defense; protein abundance alone is not enzyme flux.

Recorded consequence: STAT3 siRNA reduced SLC7A11 mRNA in the reported gallbladder cancer-cell experiments.

Scope: Human NOZ and GBC-SD gallbladder cancer cells

Solasonine did not increase STAT3 palmitoylation in the reported APT2-D13A/L11A mutant setting.

Condition: machinery_impairment · Methods 2.2 describes 48-hour cellular drug treatments with refresh at 24 hours; exact concentration must be checked per figure and is not inferred from another assay.

Normal role: GPX4 and the SLC7A11/GSH system participate in lipid peroxide defense; protein abundance alone is not enzyme flux.

Recorded consequence: Solasonine did not increase STAT3 palmitoylation in the reported APT2-D13A/L11A mutant setting.

Scope: Human NOZ and GBC-SD gallbladder cancer cells

The sources

Every document behind this chapter is preserved word for word. Open one to read it in full with its recorded conflicts marked in place.

APT2, STAT3 and GPX4: opposing branches and assay qualificationPrimary observations: 10.1038/s41467-025-56344-5 and 10.1002/ptr.70245; selected full-text review 2026-09-20. · unverified_draftRead preserved source
APT2-STAT3 cycling and a competing sulforaphane target routeSelected primary observations: 10.1038/s41586-020-2799-2 and 10.1038/s41388-020-1335-z. · unverified_draftRead preserved source
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Biotin: carboxylases, recycling, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Coenzyme Q10: biosynthesis, electron transfer, antioxidant recycling and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Copper: transport, cuproenzymes, deficiency, excess and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
DELE1 bridge: iron sensing and mitochondrial-glutathione-dependent stress signalingTargeted primary-literature curation; selected indexed full-text passages, 2026-09-20. · unverified_draftRead preserved source
DLAT: cardiac fatty-acid oxidation and mitochondrial glutathione evidenceAI-assisted two-paper curation, 2026-09-20. Cardiac full-text/supplement review; CRC abstract only. No pulmonary endothelial validation. · unverified_draftRead preserved source
Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Glutathione, ER-mitochondria contacts, and iron: observed componentsTargeted primary-literature curation, 2026-09-20. DOIs 10.1038/s41467-025-56666-4 and 10.1038/s41556-026-01974-0. · unverified_draftRead preserved source
Glutathione: metabolism, signaling and nutrient connections (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Iron: absorption, trafficking, iron-dependent enzymes and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Niacin: NAD metabolism, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
SLC16A11 and mitochondrial glutathione: published screen connection and transport evidencePrimary sources 2022 and 2017, plus labelled descriptive reanalysis on 2026-09-20. · unverified_draftRead preserved source
Selenium: literature corrections and mechanism additionsMetabolic Ledger literature curation, 17 September 2026; primary papers linked individually · secondary_verifiedRead preserved source
Sulforaphane: formation, electrophile sensing and nutrient connections (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin C: mechanisms, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source
Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17)AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · unverified_draftRead preserved source

Recorded disagreements

Where two sources say different things, both are kept and the difference is explained. You can discuss a disagreement or propose a mechanism that might account for it.

Open questions in this collection

Questions the curators could not answer from the sources in front of them, kept here with the reason each one is still open. These are gaps in this collection, not findings or proof that no one has studied them.

Which oral formulation, duration and baseline status predict tissue GSH changes?The four-week null and six-month positive trial differ in design and measurements; neither establishes universal efficacy or ineffectiveness.
Can the post-hoc GlyNAC responder subgroup be prospectively replicated?The larger two-week study had null primary endpoints; subgroup selection is not confirmed treatment personalization.
Do biomarker or physical-function signals translate into durable clinical benefit?Trials here do not establish disease prevention or lifespan extension.
How does tumor mitochondrial GSH biology relate to supplementation in people?Tumor-model carrier dependence does not establish benefit or harm from oral GSH in humans.
Does changing nutrient intake reliably increase GSH in a particular human organelle?A pathway connection, blood biomarker or whole-cell measurement cannot establish mitochondrial target engagement.
How much sulfur is diverted from remethylation to GSH synthesis under a specified human stress?B6-dependent transsulfuration is linked; B12 and folate are not consumed as stoichiometric GSH ingredients, and a universal methylation collapse is unsupported.
Does NAPQI inhibition of GSS materially cause acquired human 5-oxoprolinuric acidosis?In-vitro covalent inhibition is established; the causal contribution in patients remains unresolved.
What tissue-specific GSH supply is maintained by SLC25A39 versus SLC25A40?Cell genetics does not establish a universal share of transport or a clinical replacement strategy.

Chapters are assembled from supplied drafts and curated literature summaries. Statements remain unverified against the primary studies, and the ledger is not medical advice.

Evidence, AI assistance and curation standards

GSH

The mechanisms

Human GSS crystallized with two magnesium ions, ADP, glutathione and sulfate.

SLC25A39 loss reduced mitochondrial GSH import.

Whole-cell GSH levels were not reduced by SLC25A39 loss.

Human G6PD uses glucose-6-phosphate and catalytic NADP+ to generate NADPH.

Each GLRX5-bound [2Fe-2S] cluster was ligated by two protein Cys67 thiols and two GSH cysteine thiols.

Human hxCTb required 4F2hc for sodium-independent cystine/glutamate transport in oocytes.

CHAC1 overexpression depleted GSH in HEK293 cells; a catalytic mutation alleviated that depletion.

Eye, liver and pancreatic GSH were markedly lower in Ggt1-null mice.

Oral GSH did not significantly change erythrocyte reduced, oxidized or ratio glutathione measures.

At six months, high-dose erythrocyte GSH increased within the reported 30–35% range versus baseline.

The yeast GCL structures identified an ATP-independent magnesium coordination site associated with the enzyme’s Mg dependence.

GSH occupied the glutamate and presumed cysteine sites and disrupted ATP-site Mg coordination in the inhibited yeast structure.

The bound BSO inhibitory species was phosphorylated on its sulfoximine nitrogen.

All four mutant GCLC transfectants had lower GSH than wild type in Gclc-null mouse fibroblasts; Pro414Leu was most impaired.

Adding GCLM largely rescued impaired activity of recombinant GCLC Arg127Cys, His370Leu and Pro414Leu.

Six tested GSS variants reduced Vmax to 2–27% of wild-type activity.

GSS P314L had no major effect on the tested kinetic parameters and was classified as neutral by the investigators.

The lesion localized to GSS; findings supported excess gamma-glutamylcysteine-derived 5-oxoproline production beyond disposal capacity.

SLC25A39 loss reduced mitochondrial GSH abundance.

Combined A39/A40 loss impaired activity and stability of iron-sulfur proteins.

Targeted bacterial GshF enabled mitochondrial GSH synthesis and ameliorated proliferative defects.

An independent CRISPR/transport study identified SLC25A39 as critical for mitochondrial GSH import.

A39-mediated GSH homeostasis and A37-mediated iron uptake jointly supported OXPHOS in the genetic-interaction system.

AFG3L2 mediated SLC25A39 degradation through matrix loop 1.

Four matrix cysteines mediated iron-sulfur sensing that inhibited A39 degradation.

ATF4-responsive promoter elements supported human CHAC1 transcription in reporter experiments.

Purified human CHAC2 degraded reduced GSH with lower catalytic efficiency than CHAC1.

CHAC2 showed no activity against oxidized glutathione in the substrate comparison.

CHAC1 likewise lacked activity against GSSG in this comparison.

Human-GGT-expressing fibroblasts used extracellular GSH as a cysteine source in cysteine-free medium.

GGT-positive cells replenished intracellular GSH from extracellular GSH under cysteine deprivation; GGT-negative cells did not.

Plasma cyst(e)ine in Ggt1-null mice was about 20% of wild type.

Plasma GSH was about sixfold higher in Ggt1-null mice.

Urinary GSH was about 2500-fold higher in Ggt1-null mice.

Oral NAC restored normal growth rates in the Ggt1-null mice.

MRP1 mediated ATP-dependent GSSG transport; the HeLa-vesicle Km was 93 ± 26 micromolar.

Diethyl maleate induced xCT expression and increased cystine uptake in U87 cells.

Structural-site NADP+ binding ordered the G6PD C-terminal region and supported substrate binding and catalysis.

Apo-GLRX5 reduced glutathione mixed disulfides about 100 times more slowly than GLRX2.

GLRX2 reduced glutathionylated substrates with lower rate but higher affinity than GLRX1, giving similar catalytic efficiency.

A thioredoxin-reductase/NADPH system reduced GLRX2 disulfide and GSH-GLRX2 intermediates.

GAPDH S-glutathionylation did not itself inactivate the enzyme in this assay.

Direct hydrogen-peroxide oxidation inhibited GAPDH activity in the comparison.

Recombinant human glutaredoxin enhanced GAPDH S-glutathionylation under the tested GSSG conditions.

Human GLO1 catalyzes glutathione-dependent methylglyoxal inactivation.

The human GLO1 active site contained an essential zinc ion with ligands contributed across the dimer interface.

Human glyoxalase II hydrolyzes S-D-lactoylglutathione to GSH and D-lactate.

Human erythrocyte GLO1 forms S-D-lactoylglutathione through the methylglyoxal/GSH hemithioacetal intermediate.

Human LTC4S conjugates GSH with leukotriene A4 to make leukotriene C4.

Arg104 substitutions abolished 94.3–99.9% of LTC4S specific activity; selected variants lacked the GSH thiolate signal.

PRDX6 heterodimerization with piGST supports glutathionylation needed in the peroxidatic cycle.

The double interface mutation essentially abolished PRDX6 peroxidase activity.

The same double mutation left phospholipase A2 activity unaffected.

The activity purified from mouse macrophages metabolized GSNO and was identified as glutathione-dependent formaldehyde dehydrogenase.

Reductase deletion increased protein SNO as well as GSNO in the studied mouse system.

Human liver enzyme kinetics supported NAD+-dependent processing of S-hydroxymethylglutathione to the S-formylglutathione/NADH products.

Adding GSH decreased covalent microsomal protein binding while forming 3-S-glutathionylacetaminophen.

Cytochrome-P450-mediated acetaminophen oxidation produced NAPQI in the experimental oxidation system.

Ascorbic acid decreased binding through reduction of NAPQI to acetaminophen in the comparison.

Peptide mapping identified NAPQI binding to GSS Cys422.

NAPQI at 25–400 micromolar irreversibly reduced measured GSS activity by 16–89%.

After supplementation, older participants had a 78.8% higher fractional GSH synthesis rate.

The absolute erythrocyte GSH synthesis rate increased 230.9% after supplementation.

The older group’s erythrocyte GSH concentration increased 94.6% after supplementation.

The between-group change in urinary F2-isoprostanes was not significant (p=0.38).

The between-group change in urinary 8-OHdG was not significant (p=0.27).

At six months, high-dose plasma GSH increased within the reported 30–35% range versus baseline.

At six months, high-dose lymphocyte GSH increased within the reported 30–35% range versus baseline.

High-dose buccal-cell GSH increased about 260% versus baseline at six months.

Measured GSH levels returned to baseline after the one-month washout.

At three months, high-dose NK cytotoxicity exceeded placebo by more than twofold in the immune subset.

GlyNAC did not significantly improve the GSH:GSSG ratio; high-dose versus placebo p=0.739.

The primary total-GSH endpoint was not significantly increased; high-dose versus placebo p=0.278.

A post-hoc high-MDA/low-baseline-GSH subgroup had higher total GSH with pooled medium/high doses (p=0.016).

The older GlyNAC group improved measured GSH deficiency relative to the placebo pattern.

Investigators reported improved physical-function assessments with GlyNAC but not placebo.

A39 loss impaired early metastatic colonization in the tested breast-cancer models.

Primary tumor growth was unaffected by A39 loss in the reported comparison.