Nutrient chapter

L-Cysteine

L-Cysteine Independently recorded entity or measured process. Linked claims specify compartment, assay and experimental scope.

82 recorded mechanisms · 14 availability situations · 9 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 SLC7A9 and SLC3A1 form the b0,+AT–rBAT obligatory exchanger for cystine/cationic amino-acid influx coupled to neutral amino-acid efflux.
b0,+AT / SLC7A9 → rBAT / SLC3A1 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human transporter cryo-EM and functional study; structural ligand was arginine.
limitations
Do not describe the arginine-bound structure as a captured cystine-bound state or infer dietary competition from binding alone.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
The kidney and intestine use a two-protein exchange system to handle cystine.
primary_references
Cryo-EM structure of the human heteromeric amino acid transporter b0,+AT-rBAT. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32494597/ · DOI 10.1126/sciadv.aay6379
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 20–26
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human transporter cryo-EM and functional study; structural ligand was arginine. · source_derived_draft · unverified_draft
## l-cysteine-renal-cystine-exchange The kidney and intestine use a two-protein exchange system to handle cystine. Human SLC7A9 and SLC3A1 form the b0,+AT–rBAT obligatory exchanger for cystine/cationic amino-acid influx coupled to neutral amino-acid efflux. Model: Human transporter cryo-EM and functional study; structural ligand was arginine. Limitations: Do not describe the arginine-bound structure as a captured cystine-bound state or infer dietary competition from binding alone. Evidence access: Primary full text Cryo-EM structure of the human heteromeric amino acid transporter b0,+AT-rBAT. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32494597/ · DOI 10.1126/sciadv.aay6379
Complete structured claim and evidence
Human cystinosin structures and functional assays support proton-coupled cystine export from the lysosomal lumen toward the cytosol.
Human lysosomal cystine transporter / CTNS → Cystine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human CTNS crystallography, cryo-EM, transport and spectroscopic assays.
limitations
Transport was assayed with engineered constructs; normal dietary intake does not bypass a defective lysosomal exporter.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
Protein recycling supplies sulfur only if its breakdown products can leave the lysosome.
primary_references
Structure and mechanism of human cystine exporter cystinosin. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36113465/ · DOI 10.1016/j.cell.2022.08.020
transport_effect
raises Recorded as proton-coupled export from the lysosomal lumen toward the cytosol. The lysosomal pool falls in the same step.
transport_pool
cytosolic cystine Recorded as proton-coupled export from the lysosomal lumen toward the cytosol. The lysosomal pool falls in the same step.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 28–34
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human CTNS crystallography, cryo-EM, transport and spectroscopic assays. · source_derived_draft · unverified_draft
## l-cysteine-lysosomal-export Protein recycling supplies sulfur only if its breakdown products can leave the lysosome. Human cystinosin structures and functional assays support proton-coupled cystine export from the lysosomal lumen toward the cytosol. Model: Human CTNS crystallography, cryo-EM, transport and spectroscopic assays. Limitations: Transport was assayed with engineered constructs; normal dietary intake does not bypass a defective lysosomal exporter. Evidence access: Primary full text Structure and mechanism of human cystine exporter cystinosin. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36113465/ · DOI 10.1016/j.cell.2022.08.020
Complete structured claim and evidence
Mutating human cystinosin K273, K280, D305, W138, N166 or F142 abolished cystine transport in the reported assays.
Human CTNS substrate-binding mutations → Human lysosomal cystine transporter / CTNS source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human CTNS site-directed mutagenesis and transport measurements.
limitations
Experimental mutations and disease-associated variants are not a dietary deficiency.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
A correctly located transporter may still fail to recognize or move its substrate.
primary_references
Structure and mechanism of human cystine exporter cystinosin. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36113465/ · DOI 10.1016/j.cell.2022.08.020
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 36–42
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human CTNS site-directed mutagenesis and transport measurements. · source_derived_draft · unverified_draft
## l-cysteine-ctns-binding-residues A correctly located transporter may still fail to recognize or move its substrate. Mutating human cystinosin K273, K280, D305, W138, N166 or F142 abolished cystine transport in the reported assays. Model: Human CTNS site-directed mutagenesis and transport measurements. Limitations: Experimental mutations and disease-associated variants are not a dietary deficiency. Evidence access: Primary full text Structure and mechanism of human cystine exporter cystinosin. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36113465/ · DOI 10.1016/j.cell.2022.08.020
Complete structured claim and evidence
D346N substitution abolished the pH-dependent conformational switch; the authors proposed D346 as a key protonation site controlling human cystinosin transitions.
Proposed human CTNS D346 protonation switch → Human lysosomal cystine transporter / CTNS source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human CTNS mutagenesis and double electron–electron resonance spectroscopy at pH 5.2 and 7.4.
limitations
A structure-supported protonation model is not a demonstrated effect of changing dietary acid or mineral intake.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
The transporter couples substrate movement to an acidic compartment.
primary_references
Structure and mechanism of human cystine exporter cystinosin. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36113465/ · DOI 10.1016/j.cell.2022.08.020
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 44–50
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human CTNS mutagenesis and double electron–electron resonance spectroscopy at pH 5.2 and 7.4. · source_derived_draft · unverified_draft
## l-cysteine-ctns-proton-switch The transporter couples substrate movement to an acidic compartment. D346N substitution abolished the pH-dependent conformational switch; the authors proposed D346 as a key protonation site controlling human cystinosin transitions. Model: Human CTNS mutagenesis and double electron–electron resonance spectroscopy at pH 5.2 and 7.4. Limitations: A structure-supported protonation model is not a demonstrated effect of changing dietary acid or mineral intake. Evidence access: Primary full text Structure and mechanism of human cystine exporter cystinosin. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36113465/ · DOI 10.1016/j.cell.2022.08.020
Complete structured claim and evidence
The human CTNS N288K variant altered conformation and suppressed engagement with Ragulator–Rag, linking transporter state with a nutrient-signaling complex.
Human lysosomal cystine transporter / CTNS → Human Ragulator–Rag complex source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human cystinosin cryo-EM and interaction experiments.
limitations
This does not demonstrate that oral cysteine directly activates mTORC1.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
Transport machinery can also affect how the cell senses nutrient availability.
primary_references
Structure and mechanism of human cystine exporter cystinosin. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36113465/ · DOI 10.1016/j.cell.2022.08.020
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 52–58
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cystinosin cryo-EM and interaction experiments. · source_derived_draft · unverified_draft
## l-cysteine-ctns-ragulator Transport machinery can also affect how the cell senses nutrient availability. The human CTNS N288K variant altered conformation and suppressed engagement with Ragulator–Rag, linking transporter state with a nutrient-signaling complex. Model: Human cystinosin cryo-EM and interaction experiments. Limitations: This does not demonstrate that oral cysteine directly activates mTORC1. Evidence access: Primary full text Structure and mechanism of human cystine exporter cystinosin. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36113465/ · DOI 10.1016/j.cell.2022.08.020
Complete structured claim and evidence
TXNDC17 knockout in human HEK293 cells markedly reduced intracellular cystine reduction; wild-type TRP14 re-expression restored activity whereas its active-site mutant did not.
Human thioredoxin-related protein 14 / TXNDC17 → L-Cysteine source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human HEK293 knockout/rescue; fluorescent cystine-reduction assays.
limitations
The paper identifies a major rate-limiting route in tested systems, not the only possible reductase in every tissue.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
Importing oxidized cysteine is not enough: the cell must reduce it to use it.
primary_references
TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38811853/ · DOI 10.1038/s44318-024-00117-1
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 60–66
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human HEK293 knockout/rescue; fluorescent cystine-reduction assays. · source_derived_draft · unverified_draft
## l-cysteine-trp14-cystine-reduction Importing oxidized cysteine is not enough: the cell must reduce it to use it. TXNDC17 knockout in human HEK293 cells markedly reduced intracellular cystine reduction; wild-type TRP14 re-expression restored activity whereas its active-site mutant did not. Model: Human HEK293 knockout/rescue; fluorescent cystine-reduction assays. Limitations: The paper identifies a major rate-limiting route in tested systems, not the only possible reductase in every tissue. Evidence access: Primary full text TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38811853/ · DOI 10.1038/s44318-024-00117-1
Complete structured claim and evidence
The reconstituted TRP14 system used thioredoxin reductase 1 and NADPH to drive disulfide-reduction reactions.
TXNRD1 → Human thioredoxin-related protein 14 / TXNDC17 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Purified enzyme systems, including human peroxiredoxin-2 decysteinylation.
limitations
This establishes a biochemical dependency; selenium or niacin depletion/repletion was not tested in this study.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
The sulfur-supply step depends on an electron supply and another enzyme.
primary_references
TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38811853/ · DOI 10.1038/s44318-024-00117-1
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 68–74
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified enzyme systems, including human peroxiredoxin-2 decysteinylation. · source_derived_draft · unverified_draft
## l-cysteine-trp14-electron-supply The sulfur-supply step depends on an electron supply and another enzyme. The reconstituted TRP14 system used thioredoxin reductase 1 and NADPH to drive disulfide-reduction reactions. Model: Purified enzyme systems, including human peroxiredoxin-2 decysteinylation. Limitations: This establishes a biochemical dependency; selenium or niacin depletion/repletion was not tested in this study. Evidence access: Primary full text TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38811853/ · DOI 10.1038/s44318-024-00117-1
Complete structured claim and evidence
TXNDC17 knockout shifted human-cell cysteine supply toward transsulfuration, as assessed using labeled methionine and downstream sulfur metabolites.
Human TXNDC17 loss → Human-cell cysteine supply through transsulfuration source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human HEK293 metabolic tracing and enzyme perturbation.
limitations
Compensation requires intact transsulfuration and does not prove that B6 supplementation rescues every transport defect.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
An internal synthesis route compensated when imported cystine was harder to use.
primary_references
TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38811853/ · DOI 10.1038/s44318-024-00117-1
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 76–82
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human HEK293 metabolic tracing and enzyme perturbation. · source_derived_draft · unverified_draft
## l-cysteine-trp14-compensation An internal synthesis route compensated when imported cystine was harder to use. TXNDC17 knockout shifted human-cell cysteine supply toward transsulfuration, as assessed using labeled methionine and downstream sulfur metabolites. Model: Human HEK293 metabolic tracing and enzyme perturbation. Limitations: Compensation requires intact transsulfuration and does not prove that B6 supplementation rescues every transport defect. Evidence access: Primary full text TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38811853/ · DOI 10.1038/s44318-024-00117-1
Complete structured claim and evidence
TRP14 removed cysteinyl mixed-disulfide modifications from human peroxiredoxin 2 and restored its peroxide-reducing activity in vitro.
Human thioredoxin-related protein 14 / TXNDC17 → Human peroxiredoxin 2 / PRDX2 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Recombinant human Prx2; cysteinylation and hydrogen-peroxide reduction assays.
limitations
TRP14 repairs this modification; it is not being assigned the ordinary catalytic peroxide-reduction cycle of thioredoxin.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
A cysteine modification can temporarily obstruct another antioxidant enzyme.
primary_references
TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38811853/ · DOI 10.1038/s44318-024-00117-1
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 84–90
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human Prx2; cysteinylation and hydrogen-peroxide reduction assays. · source_derived_draft · unverified_draft
## l-cysteine-protein-decysteinylation A cysteine modification can temporarily obstruct another antioxidant enzyme. TRP14 removed cysteinyl mixed-disulfide modifications from human peroxiredoxin 2 and restored its peroxide-reducing activity in vitro. Model: Recombinant human Prx2; cysteinylation and hydrogen-peroxide reduction assays. Limitations: TRP14 repairs this modification; it is not being assigned the ordinary catalytic peroxide-reduction cycle of thioredoxin. Evidence access: Primary full text TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38811853/ · DOI 10.1038/s44318-024-00117-1
Complete structured claim and evidence
Txndc17 knockout mice showed protection in the acute pancreatitis model, accompanied by Nrf2-pathway activation and increased transsulfuration.
Mouse Txndc17 loss → Acute pancreatitis injury in mouse Txndc17 experiments source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Mouse genetic deletion and experimental acute pancreatitis.
limitations
Not a recommendation to inhibit TRP14; the finding does not contradict its cystine-reduction role.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
An enzyme defect can trigger protective compensation in a specific stress model.
primary_references
TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38811853/ · DOI 10.1038/s44318-024-00117-1
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 92–98
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse genetic deletion and experimental acute pancreatitis. · source_derived_draft · unverified_draft
## l-cysteine-trp14-mouse-adaptation An enzyme defect can trigger protective compensation in a specific stress model. Txndc17 knockout mice showed protection in the acute pancreatitis model, accompanied by Nrf2-pathway activation and increased transsulfuration. Model: Mouse genetic deletion and experimental acute pancreatitis. Limitations: Not a recommendation to inhibit TRP14; the finding does not contradict its cystine-reduction role. Evidence access: Primary full text TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38811853/ · DOI 10.1038/s44318-024-00117-1
Complete structured claim and evidence
Slc1a1-null mice had lower neuronal glutathione, increased oxidant susceptibility and age-dependent brain atrophy and behavioral changes.
Mouse EAAT3 / Slc1a1 → Mouse neuronal glutathione pool source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse EAAC1 gene deletion, hippocampal slices and aging observations.
limitations
Does not establish a human oral cysteine treatment or make neuronal and astrocytic transport interchangeable.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
A neuron can lack usable cysteine even when the amino acid exists elsewhere.
primary_references
Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16311588/ · DOI 10.1038/nn1609
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 100–106
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse EAAC1 gene deletion, hippocampal slices and aging observations. · source_derived_draft · unverified_draft
## l-cysteine-neuronal-uptake-gate A neuron can lack usable cysteine even when the amino acid exists elsewhere. Slc1a1-null mice had lower neuronal glutathione, increased oxidant susceptibility and age-dependent brain atrophy and behavioral changes. Model: Mouse EAAC1 gene deletion, hippocampal slices and aging observations. Limitations: Does not establish a human oral cysteine treatment or make neuronal and astrocytic transport interchangeable. Evidence access: Primary abstract Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16311588/ · DOI 10.1038/nn1609
Complete structured claim and evidence
N-acetylcysteine treatment reversed reduced neuronal glutathione and oxidant-related abnormalities in EAAC1-deficient mice.
N-Acetyl-L-cysteine → Mouse neuronal glutathione pool source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse Slc1a1 deletion with NAC treatment.
limitations
NAC is the tested intervention, not free L-cysteine; no human cognitive benefit is established.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
A different precursor bypassed part of the uptake limitation in this animal model.
primary_references
Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16311588/ · DOI 10.1038/nn1609
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 108–114
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse Slc1a1 deletion with NAC treatment. · source_derived_draft · unverified_draft
## l-cysteine-nac-neuronal-rescue A different precursor bypassed part of the uptake limitation in this animal model. N-acetylcysteine treatment reversed reduced neuronal glutathione and oxidant-related abnormalities in EAAC1-deficient mice. Model: Mouse Slc1a1 deletion with NAC treatment. Limitations: NAC is the tested intervention, not free L-cysteine; no human cognitive benefit is established. Evidence access: Primary abstract Neuronal glutathione deficiency and age-dependent neurodegeneration in the EAAC1 deficient mouse. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16311588/ · DOI 10.1038/nn1609
Complete structured claim and evidence
EAAC1-null mice had increased vesicular/cytosolic hippocampal zinc and greater zinc redistribution and neuronal injury after transient cerebral ischemia.
Mouse EAAC1 loss → Labile zinc in mouse hippocampal neurons source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse knockout, zinc measurements and transient ischemia.
limitations
The experiment did not test dietary zinc deficiency or toxicity thresholds.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
Impaired cysteine supply affected metal handling as well as antioxidant capacity.
primary_references
EAAC1 gene deletion alters zinc homeostasis and exacerbates neuronal injury after transient cerebral ischemia. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21084597/ · DOI 10.1523/JNEUROSCI.2084-10.2010
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 116–122
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse knockout, zinc measurements and transient ischemia. · source_derived_draft · unverified_draft
## l-cysteine-neuronal-zinc-link Impaired cysteine supply affected metal handling as well as antioxidant capacity. EAAC1-null mice had increased vesicular/cytosolic hippocampal zinc and greater zinc redistribution and neuronal injury after transient cerebral ischemia. Model: Mouse knockout, zinc measurements and transient ischemia. Limitations: The experiment did not test dietary zinc deficiency or toxicity thresholds. Evidence access: Primary abstract EAAC1 gene deletion alters zinc homeostasis and exacerbates neuronal injury after transient cerebral ischemia. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21084597/ · DOI 10.1523/JNEUROSCI.2084-10.2010
Complete structured claim and evidence
NAC restored neuronal glutathione and normalized basal zinc levels in EAAC1-null mice; NAC or zinc chelation reduced ischemia-associated zinc movement, superoxide and neuronal death.
N-Acetyl-L-cysteine → Labile zinc in mouse hippocampal neurons source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse EAAC1-null ischemia model.
limitations
NAC and chelators are separate interventions; the study does not show that extra dietary cysteine and zinc are synergistic.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
Restoring precursor supply and binding excess labile zinc were distinct rescue routes.
primary_references
EAAC1 gene deletion alters zinc homeostasis and exacerbates neuronal injury after transient cerebral ischemia. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21084597/ · DOI 10.1523/JNEUROSCI.2084-10.2010
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 124–130
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse EAAC1-null ischemia model. · source_derived_draft · unverified_draft
## l-cysteine-neuronal-zinc-rescue Restoring precursor supply and binding excess labile zinc were distinct rescue routes. NAC restored neuronal glutathione and normalized basal zinc levels in EAAC1-null mice; NAC or zinc chelation reduced ischemia-associated zinc movement, superoxide and neuronal death. Model: Mouse EAAC1-null ischemia model. Limitations: NAC and chelators are separate interventions; the study does not show that extra dietary cysteine and zinc are synergistic. Evidence access: Primary abstract EAAC1 gene deletion alters zinc homeostasis and exacerbates neuronal injury after transient cerebral ischemia. · 2010 · https://pubmed.ncbi.nlm.nih.gov/21084597/ · DOI 10.1523/JNEUROSCI.2084-10.2010
Complete structured claim and evidence
Cysteine scarcity promoted CARS association with AMPK gamma-2, whereas cysteine inhibited this association in the reported experiments.
Human cytosolic cysteinyl-tRNA synthetase / CARS1 → Human AMPK gamma-2 / PRKAG2 source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary abstract and indexed primary figure descriptions
experimental_model
Human 293T-centered cell and binding experiments; extracellular cystine withdrawal or 0–200 micromolar titration for eight hours.
limitations
Medium cystine manipulation changes intracellular cysteine; do not relabel it as a controlled human dietary intake.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
A protein-synthesis enzyme also helped sense the availability of its amino acid.
primary_references
CARS senses cysteine deprivation to activate AMPK for cell survival. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34472622/ · DOI 10.15252/embj.2021108028
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 132–138
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human 293T-centered cell and binding experiments; extracellular cystine withdrawal or 0–200 micromolar titration for eight hours. · source_derived_draft · unverified_draft
## l-cysteine-cars-sensing A protein-synthesis enzyme also helped sense the availability of its amino acid. Cysteine scarcity promoted CARS association with AMPK gamma-2, whereas cysteine inhibited this association in the reported experiments. Model: Human 293T-centered cell and binding experiments; extracellular cystine withdrawal or 0–200 micromolar titration for eight hours. Limitations: Medium cystine manipulation changes intracellular cysteine; do not relabel it as a controlled human dietary intake. Evidence access: Primary abstract and indexed primary figure descriptions CARS senses cysteine deprivation to activate AMPK for cell survival. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34472622/ · DOI 10.15252/embj.2021108028
Complete structured claim and evidence
Under cysteine-deficient conditions, CARS promoted AMPK association with CaMKK2 and CaMKK2-dependent AMPK phosphorylation.
Human cytosolic cysteinyl-tRNA synthetase / CARS1 → Human calcium/calmodulin-dependent protein kinase kinase 2 / CAMKK2 source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary abstract and indexed primary figure descriptions
experimental_model
Human 293T and cancer-cell experimental program.
limitations
CaMKK2 identity does not by itself show dietary calcium depletion or calcium-supplement rescue.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
The sensing protein helped bring a kinase and its target together.
primary_references
CARS senses cysteine deprivation to activate AMPK for cell survival. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34472622/ · DOI 10.15252/embj.2021108028
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 140–146
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human 293T and cancer-cell experimental program. · source_derived_draft · unverified_draft
## l-cysteine-cars-camkk2-bridge The sensing protein helped bring a kinase and its target together. Under cysteine-deficient conditions, CARS promoted AMPK association with CaMKK2 and CaMKK2-dependent AMPK phosphorylation. Model: Human 293T and cancer-cell experimental program. Limitations: CaMKK2 identity does not by itself show dietary calcium depletion or calcium-supplement rescue. Evidence access: Primary abstract and indexed primary figure descriptions CARS senses cysteine deprivation to activate AMPK for cell survival. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34472622/ · DOI 10.15252/embj.2021108028
Complete structured claim and evidence
Blocking AMPK activation increased cell death under cysteine-deficient conditions in the tested cultures.
Human AMP-activated protein kinase complexes → Survival of cysteine-starved human cells source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human-cell nutrient-withdrawal experiments with AMPK-pathway perturbation.
limitations
This is an adaptive response under culture deprivation, not evidence that chronic dietary deprivation is beneficial.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
The response to scarcity helped cells survive it.
primary_references
CARS senses cysteine deprivation to activate AMPK for cell survival. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34472622/ · DOI 10.15252/embj.2021108028
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 148–154
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human-cell nutrient-withdrawal experiments with AMPK-pathway perturbation. · source_derived_draft · unverified_draft
## l-cysteine-ampk-adaptation The response to scarcity helped cells survive it. Blocking AMPK activation increased cell death under cysteine-deficient conditions in the tested cultures. Model: Human-cell nutrient-withdrawal experiments with AMPK-pathway perturbation. Limitations: This is an adaptive response under culture deprivation, not evidence that chronic dietary deprivation is beneficial. Evidence access: Primary abstract CARS senses cysteine deprivation to activate AMPK for cell survival. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34472622/ · DOI 10.15252/embj.2021108028
Complete structured claim and evidence
CARS2 disruption reduced mitochondrial cysteinyl-tRNA synthetase function, assessed in part through mitochondrial MTCO1 expression; mutant rescue distinguished this from persulfide synthesis.
Human mitochondrial cysteinyl-tRNA synthetase / CARS2 → Human mitochondrial cysteine incorporation during translation source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human HEK293T CARS2-deficient cells and C78/257D versus lysine-motif mutant complementation.
limitations
MTCO1 expression is a translation-related readout, not a direct measurement of dietary cysteine incorporation.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
Mitochondria need their own enzyme to place cysteine into proteins.
primary_references
Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29079736/ · DOI 10.1038/s41467-017-01311-y
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 156–162
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human HEK293T CARS2-deficient cells and C78/257D versus lysine-motif mutant complementation. · source_derived_draft · unverified_draft
## l-cysteine-cars2-translation Mitochondria need their own enzyme to place cysteine into proteins. CARS2 disruption reduced mitochondrial cysteinyl-tRNA synthetase function, assessed in part through mitochondrial MTCO1 expression; mutant rescue distinguished this from persulfide synthesis. Model: Human HEK293T CARS2-deficient cells and C78/257D versus lysine-motif mutant complementation. Limitations: MTCO1 expression is a translation-related readout, not a direct measurement of dietary cysteine incorporation. Evidence access: Primary full text Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29079736/ · DOI 10.1038/s41467-017-01311-y
Complete structured claim and evidence
CARS2 disruption lowered cysteine-persulfide production in human cells, and wild-type or the C78/257D mutant restored it despite differing effects on translation.
Human mitochondrial cysteinyl-tRNA synthetase / CARS2 → Cysteine persulfide / CysSSH source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human HEK293T knockout/rescue and LC–MS/MS persulfide assays.
limitations
Assay and mutation-dependent evidence; the proposed importance of this route is not proof of identical dominance in all human tissues.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
One enzyme had separable roles in protein synthesis and sulfur chemistry.
primary_references
Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29079736/ · DOI 10.1038/s41467-017-01311-y
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 164–170
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human HEK293T knockout/rescue and LC–MS/MS persulfide assays. · source_derived_draft · unverified_draft
## l-cysteine-cars2-persulfide One enzyme had separable roles in protein synthesis and sulfur chemistry. CARS2 disruption lowered cysteine-persulfide production in human cells, and wild-type or the C78/257D mutant restored it despite differing effects on translation. Model: Human HEK293T knockout/rescue and LC–MS/MS persulfide assays. Limitations: Assay and mutation-dependent evidence; the proposed importance of this route is not proof of identical dominance in all human tissues. Evidence access: Primary full text Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29079736/ · DOI 10.1038/s41467-017-01311-y
Complete structured claim and evidence
CARS2-deficient human cells had fragmented or shrunken mitochondria; re-expression of wild-type or persulfide-competent C78/257D CARS2 improved morphology, unlike the tested persulfide-impaired lysine mutants.
Human mitochondrial cysteinyl-tRNA synthetase / CARS2 → Mitochondrial morphology in human CARS2-deficient cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human HEK293T imaging and mutant rescue.
limitations
This does not show that free-cysteine supplementation repairs mitochondrial disease.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
Sulfur chemistry contributed to mitochondrial behavior beyond protein production.
primary_references
Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29079736/ · DOI 10.1038/s41467-017-01311-y
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 172–178
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human HEK293T imaging and mutant rescue. · source_derived_draft · unverified_draft
## l-cysteine-cars2-mitochondrial-shape Sulfur chemistry contributed to mitochondrial behavior beyond protein production. CARS2-deficient human cells had fragmented or shrunken mitochondria; re-expression of wild-type or persulfide-competent C78/257D CARS2 improved morphology, unlike the tested persulfide-impaired lysine mutants. Model: Human HEK293T imaging and mutant rescue. Limitations: This does not show that free-cysteine supplementation repairs mitochondrial disease. Evidence access: Primary full text Cysteinyl-tRNA synthetase governs cysteine polysulfidation and mitochondrial bioenergetics. · 2017 · https://pubmed.ncbi.nlm.nih.gov/29079736/ · DOI 10.1038/s41467-017-01311-y
Complete structured claim and evidence
Cystine starvation induced lipid oxidation and ferroptosis in four of five tested human PDAC cell lines.
Cystine → Ferroptosis in human pancreatic cancer models source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human pancreatic cancer cultures; nutrient withdrawal, oxidation and viability assays.
limitations
Culture starvation is not dietary treatment; one of the tested lines differed.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
Dependence on external sulfur varied between cancer-cell models.
primary_references
Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 180–186
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human pancreatic cancer cultures; nutrient withdrawal, oxidation and viability assays. · source_derived_draft · unverified_draft
## l-cysteine-pdac-cystine-withdrawal Dependence on external sulfur varied between cancer-cell models. Cystine starvation induced lipid oxidation and ferroptosis in four of five tested human PDAC cell lines. Model: Human pancreatic cancer cultures; nutrient withdrawal, oxidation and viability assays. Limitations: Culture starvation is not dietary treatment; one of the tested lines differed. Evidence access: Primary full text Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872
Complete structured claim and evidence
Carbon-13 cystine tracing showed labeling of glutathione and CoA over the experiment, including CoA labeling over 24 hours.
Cystine → Coenzyme A source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human PDAC stable-isotope tracing.
limitations
No labeling of taurine, lactate, citrate or glutamate was detected in these assays; that does not abolish those routes in other tissues.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
Cysteine-derived material entered more than one protective metabolic pool.
primary_references
Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 188–194
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PDAC stable-isotope tracing. · source_derived_draft · unverified_draft
## l-cysteine-pdac-carbon-tracing Cysteine-derived material entered more than one protective metabolic pool. Carbon-13 cystine tracing showed labeling of glutathione and CoA over the experiment, including CoA labeling over 24 hours. Model: Human PDAC stable-isotope tracing. Limitations: No labeling of taurine, lactate, citrate or glutamate was detected in these assays; that does not abolish those routes in other tissues. Evidence access: Primary full text Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872
Complete structured claim and evidence
System xc− inhibition lowered CoA and increased upstream pantothenate in the tested pancreatic cancer cells.
SLC7A11 → Coenzyme A source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human PDAC cultures with cystine-import inhibition and metabolomics.
limitations
Pantothenate accumulation is not proof of B5 toxicity or a clinical biomarker threshold.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
Vitamin B5 could accumulate while its downstream product fell because another substrate was missing.
primary_references
Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 196–202
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PDAC cultures with cystine-import inhibition and metabolomics. · source_derived_draft · unverified_draft
## l-cysteine-pdac-coa-branch Vitamin B5 could accumulate while its downstream product fell because another substrate was missing. System xc− inhibition lowered CoA and increased upstream pantothenate in the tested pancreatic cancer cells. Model: Human PDAC cultures with cystine-import inhibition and metabolomics. Limitations: Pantothenate accumulation is not proof of B5 toxicity or a clinical biomarker threshold. Evidence access: Primary full text Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872
Complete structured claim and evidence
Buthionine sulfoximine lowered glutathione without inducing lipid oxidation or loss of viability under the tested PDAC conditions.
GSH synthesis inhibition with BSO in PDAC cells → Ferroptosis in human pancreatic cancer models source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human PDAC cultures, BSO and viability/lipid-ROS assays.
limitations
This null result is model-specific; it does not make glutathione dispensable in general.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
Loss of glutathione alone did not explain the whole cysteine-depletion effect.
primary_references
Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 204–210
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PDAC cultures, BSO and viability/lipid-ROS assays. · source_derived_draft · unverified_draft
## l-cysteine-pdac-gsh-only-limit Loss of glutathione alone did not explain the whole cysteine-depletion effect. Buthionine sulfoximine lowered glutathione without inducing lipid oxidation or loss of viability under the tested PDAC conditions. Model: Human PDAC cultures, BSO and viability/lipid-ROS assays. Limitations: This null result is model-specific; it does not make glutathione dispensable in general. Evidence access: Primary full text Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872
Complete structured claim and evidence
Pantothenate-kinase inhibition combined with BSO synergistically induced ferroptosis in the reported PDAC assays.
Combined pantothenate-kinase and GSH-synthesis inhibition → Ferroptosis in human pancreatic cancer models source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human PDAC culture; pharmacological PANKi/BSO combination.
limitations
This is a demonstrated drug-combination interaction in this assay, not evidence for oral B5/cysteine supplement synergy.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
Two protective branches were experimentally blocked together.
primary_references
Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 212–218
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PDAC culture; pharmacological PANKi/BSO combination. · source_derived_draft · unverified_draft
## l-cysteine-pdac-dual-block Two protective branches were experimentally blocked together. Pantothenate-kinase inhibition combined with BSO synergistically induced ferroptosis in the reported PDAC assays. Model: Human PDAC culture; pharmacological PANKi/BSO combination. Limitations: This is a demonstrated drug-combination interaction in this assay, not evidence for oral B5/cysteine supplement synergy. Evidence access: Primary full text Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872
Complete structured claim and evidence
Adding CoA prevented ferroptosis induced by imidazole ketone erastin in the reported PDAC cell experiments.
Coenzyme A → Ferroptosis in human pancreatic cancer models source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human PDAC culture and exogenous CoA treatment.
limitations
Cell-culture rescue does not establish oral CoA absorption, intact cellular uptake in vivo or clinical efficacy.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
Restoring a downstream metabolite bypassed part of an upstream block in culture.
primary_references
Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 220–226
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human PDAC culture and exogenous CoA treatment. · source_derived_draft · unverified_draft
## l-cysteine-pdac-coa-rescue Restoring a downstream metabolite bypassed part of an upstream block in culture. Adding CoA prevented ferroptosis induced by imidazole ketone erastin in the reported PDAC cell experiments. Model: Human PDAC culture and exogenous CoA treatment. Limitations: Cell-culture rescue does not establish oral CoA absorption, intact cellular uptake in vivo or clinical efficacy. Evidence access: Primary full text Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872
Complete structured claim and evidence
Deleting Slc7a11 in established genetically engineered mouse PDAC induced tumor-selective ferroptosis and inhibited growth.
Mouse cystine/glutamate antiporter / Slc7a11 → Cystine-dependent growth of mouse pancreatic tumors source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Genetically engineered mice with established pancreatic tumors.
limitations
Not all tumors or normal tissues have the same dependency; dietary deprivation was not this intervention.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
A transporter dependency could be targeted in this animal cancer model.
primary_references
Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 228–234
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Genetically engineered mice with established pancreatic tumors. · source_derived_draft · unverified_draft
## l-cysteine-mouse-pdac-import-loss A transporter dependency could be targeted in this animal cancer model. Deleting Slc7a11 in established genetically engineered mouse PDAC induced tumor-selective ferroptosis and inhibited growth. Model: Genetically engineered mice with established pancreatic tumors. Limitations: Not all tumors or normal tissues have the same dependency; dietary deprivation was not this intervention. Evidence access: Primary full text Cysteine depletion induces pancreatic tumor ferroptosis in mice. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32241947/ · DOI 10.1126/science.aaw9872
Complete structured claim and evidence
High SLC7A11-mediated cystine uptake increased reliance on glucose and the pentose phosphate pathway; glucose deprivation depleted NADPH and promoted intracellular disulfide accumulation.
SLC7A11 → Disulfide stress in SLC7A11-high human cells source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human cancer-cell transporter manipulation, glucose withdrawal and metabolic assays.
limitations
Complete glucose withdrawal in culture is not ordinary fasting or dietary carbohydrate restriction.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
Importing more oxidized nutrient also creates more work for the reducing system.
primary_references
Cystine transporter regulation of pentose phosphate pathway dependency and disulfide stress exposes a targetable metabolic vulnerability in cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32231310/ · DOI 10.1038/s41556-020-0496-x
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 236–242
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell transporter manipulation, glucose withdrawal and metabolic assays. · source_derived_draft · unverified_draft
## l-cysteine-cystine-nadph-demand Importing more oxidized nutrient also creates more work for the reducing system. High SLC7A11-mediated cystine uptake increased reliance on glucose and the pentose phosphate pathway; glucose deprivation depleted NADPH and promoted intracellular disulfide accumulation. Model: Human cancer-cell transporter manipulation, glucose withdrawal and metabolic assays. Limitations: Complete glucose withdrawal in culture is not ordinary fasting or dietary carbohydrate restriction. Evidence access: Primary full text Cystine transporter regulation of pentose phosphate pathway dependency and disulfide stress exposes a targetable metabolic vulnerability in cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32231310/ · DOI 10.1038/s41556-020-0496-x
Complete structured claim and evidence
Preventing cystine uptake or removing cystine relieved the disulfide stress associated with glucose deprivation in SLC7A11-high cells.
Cystine removal during glucose starvation → Disulfide stress in SLC7A11-high human cells source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human cancer-cell glucose/cystine manipulation.
limitations
This is distinct from cystine-withdrawal ferroptosis under other conditions; no universal benefit of removing cystine is implied.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
Reducing the incoming load helped when the cell could not process it.
primary_references
Cystine transporter regulation of pentose phosphate pathway dependency and disulfide stress exposes a targetable metabolic vulnerability in cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32231310/ · DOI 10.1038/s41556-020-0496-x
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 244–250
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell glucose/cystine manipulation. · source_derived_draft · unverified_draft
## l-cysteine-cystine-reduction-rescue Reducing the incoming load helped when the cell could not process it. Preventing cystine uptake or removing cystine relieved the disulfide stress associated with glucose deprivation in SLC7A11-high cells. Model: Human cancer-cell glucose/cystine manipulation. Limitations: This is distinct from cystine-withdrawal ferroptosis under other conditions; no universal benefit of removing cystine is implied. Evidence access: Primary full text Cystine transporter regulation of pentose phosphate pathway dependency and disulfide stress exposes a targetable metabolic vulnerability in cancer. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32231310/ · DOI 10.1038/s41556-020-0496-x
Complete structured claim and evidence
Glucose starvation of SLC7A11-high human cancer cells induced abnormal disulfide bonding in actin-cytoskeleton proteins, F-actin collapse and disulfidptosis, distinct from apoptosis and ferroptosis.
Disulfide stress in SLC7A11-high human cells → Actin-cytoskeleton disulfide bonding and collapse in human cells source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary abstract and primary publisher figure descriptions
experimental_model
Human cancer cultures, chemical proteomics and cell-biological assays.
limitations
Experimental deprivation; do not infer this occurs whenever blood glucose falls modestly.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
The damage involved cross-linked structural proteins rather than the same lipid-peroxide pathway.
primary_references
Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36747082/ · DOI 10.1038/s41556-023-01091-2
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 252–258
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer cultures, chemical proteomics and cell-biological assays. · source_derived_draft · unverified_draft
## l-cysteine-disulfidptosis-actin The damage involved cross-linked structural proteins rather than the same lipid-peroxide pathway. Glucose starvation of SLC7A11-high human cancer cells induced abnormal disulfide bonding in actin-cytoskeleton proteins, F-actin collapse and disulfidptosis, distinct from apoptosis and ferroptosis. Model: Human cancer cultures, chemical proteomics and cell-biological assays. Limitations: Experimental deprivation; do not infer this occurs whenever blood glucose falls modestly. Evidence access: Primary abstract and primary publisher figure descriptions Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36747082/ · DOI 10.1038/s41556-023-01091-2
Complete structured claim and evidence
Inactivation of the WAVE regulatory complex suppressed disulfidptosis, whereas constitutive Rac activation promoted it in the studied cells.
Human WAVE regulatory complex → Actin-cytoskeleton disulfide bonding and collapse in human cells source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Human cancer-cell CRISPR screens and functional perturbations.
limitations
A complex-level finding is not assigned to every WAVE subunit or Rac isoform without resolution.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
The state of the actin-assembly machinery changed vulnerability to sulfur stress.
primary_references
Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36747082/ · DOI 10.1038/s41556-023-01091-2
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 260–266
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell CRISPR screens and functional perturbations. · source_derived_draft · unverified_draft
## l-cysteine-disulfidptosis-wave The state of the actin-assembly machinery changed vulnerability to sulfur stress. Inactivation of the WAVE regulatory complex suppressed disulfidptosis, whereas constitutive Rac activation promoted it in the studied cells. Model: Human cancer-cell CRISPR screens and functional perturbations. Limitations: A complex-level finding is not assigned to every WAVE subunit or Rac isoform without resolution. Evidence access: Primary abstract Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis. · 2023 · https://pubmed.ncbi.nlm.nih.gov/36747082/ · DOI 10.1038/s41556-023-01091-2
Complete structured claim and evidence
Sulfur-35 cysteine supplied sulfur for newly assembled iron–sulfur clusters incorporated into aconitase and ferredoxins in isolated mouse neuronal-cell mitochondria.
L-Cysteine → Iron–sulfur cluster assembly in isolated mouse-cell mitochondria source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mitochondria from mouse Cath.A-derived neuronal cells; radioactive sulfur tracing.
limitations
An isolated-organelle assembly assay is not evidence that more dietary cysteine corrects an iron–sulfur disease.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
Cysteine supplies the sulfur half of an iron–sulfur cofactor.
primary_references
Fe-S cluster biogenesis in isolated mammalian mitochondria: coordinated use of persulfide sulfur and iron and requirements for GTP, NADH, and ATP. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25398879/ · DOI 10.1074/jbc.M114.610402
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 268–274
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mitochondria from mouse Cath.A-derived neuronal cells; radioactive sulfur tracing. · source_derived_draft · unverified_draft
## l-cysteine-fe-s-sulfur-donor Cysteine supplies the sulfur half of an iron–sulfur cofactor. Sulfur-35 cysteine supplied sulfur for newly assembled iron–sulfur clusters incorporated into aconitase and ferredoxins in isolated mouse neuronal-cell mitochondria. Model: Mitochondria from mouse Cath.A-derived neuronal cells; radioactive sulfur tracing. Limitations: An isolated-organelle assembly assay is not evidence that more dietary cysteine corrects an iron–sulfur disease. Evidence access: Primary abstract Fe-S cluster biogenesis in isolated mammalian mitochondria: coordinated use of persulfide sulfur and iron and requirements for GTP, NADH, and ATP. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25398879/ · DOI 10.1074/jbc.M114.610402
Complete structured claim and evidence
Labeled NFS1-bound persulfide was an intermediate; its sulfur release required iron, GTP and NADH, whereas ATP was required for the overall assembly pathway but not this release step.
Mouse cysteine desulfurase / Nfs1 → Iron–sulfur cluster assembly in isolated mouse-cell mitochondria source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse-cell isolated mitochondrial experiments.
limitations
The proposed GTPase/reductase mediators were not individually established by this study; do not assign a universal ATP requirement to each substep.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
The pathway has several gates, with different requirements at different steps.
primary_references
Fe-S cluster biogenesis in isolated mammalian mitochondria: coordinated use of persulfide sulfur and iron and requirements for GTP, NADH, and ATP. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25398879/ · DOI 10.1074/jbc.M114.610402
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 276–282
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse-cell isolated mitochondrial experiments. · source_derived_draft · unverified_draft
## l-cysteine-nfs1-persulfide-gate The pathway has several gates, with different requirements at different steps. Labeled NFS1-bound persulfide was an intermediate; its sulfur release required iron, GTP and NADH, whereas ATP was required for the overall assembly pathway but not this release step. Model: Mouse-cell isolated mitochondrial experiments. Limitations: The proposed GTPase/reductase mediators were not individually established by this study; do not assign a universal ATP requirement to each substep. Evidence access: Primary abstract Fe-S cluster biogenesis in isolated mammalian mitochondria: coordinated use of persulfide sulfur and iron and requirements for GTP, NADH, and ATP. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25398879/ · DOI 10.1074/jbc.M114.610402
Complete structured claim and evidence
Purified human CBS favored H2S production through replacement of cysteine by homocysteine over the tested alternative cysteine reactions.
Human cystathionine beta-synthase / CBS → L-Cysteine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human and yeast CBS kinetics, with human enzyme kept as this record’s subject.
limitations
Relative pathway dominance in a tissue cannot be read directly from purified-enzyme substrate tests.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
An enzyme that helps synthesize cysteine can also use it in sulfur-gas production.
primary_references
Relative contributions of cystathionine beta-synthase and gamma-cystathionase to H2S biogenesis via alternative trans-sulfuration reactions. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19531479/ · DOI 10.1074/jbc.M109.010868
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 284–290
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human and yeast CBS kinetics, with human enzyme kept as this record’s subject. · source_derived_draft · unverified_draft
## l-cysteine-cbs-h2s-branch An enzyme that helps synthesize cysteine can also use it in sulfur-gas production. Purified human CBS favored H2S production through replacement of cysteine by homocysteine over the tested alternative cysteine reactions. Model: Human and yeast CBS kinetics, with human enzyme kept as this record’s subject. Limitations: Relative pathway dominance in a tissue cannot be read directly from purified-enzyme substrate tests. Evidence access: Primary abstract Relative contributions of cystathionine beta-synthase and gamma-cystathionase to H2S biogenesis via alternative trans-sulfuration reactions. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19531479/ · DOI 10.1074/jbc.M109.010868
Complete structured claim and evidence
Kinetic simulations predicted that SAM-dependent activation changes the relative CBS contribution to H2S generation at specified substrate concentrations.
S-Adenosyl-L-methionine → Human cystathionine beta-synthase / CBS source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Simulation based on purified CBS/CSE kinetics with assumed equimolar enzyme concentrations.
limitations
A modeled 25–70% contribution is not a directly measured universal human tissue fraction.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
Methylation-cycle chemistry can influence a sulfur-signaling branch.
primary_references
Relative contributions of cystathionine beta-synthase and gamma-cystathionase to H2S biogenesis via alternative trans-sulfuration reactions. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19531479/ · DOI 10.1074/jbc.M109.010868
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 292–298
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Simulation based on purified CBS/CSE kinetics with assumed equimolar enzyme concentrations. · source_derived_draft · unverified_draft
## l-cysteine-sam-sulfur-partition Methylation-cycle chemistry can influence a sulfur-signaling branch. Kinetic simulations predicted that SAM-dependent activation changes the relative CBS contribution to H2S generation at specified substrate concentrations. Model: Simulation based on purified CBS/CSE kinetics with assumed equimolar enzyme concentrations. Limitations: A modeled 25–70% contribution is not a directly measured universal human tissue fraction. Evidence access: Primary abstract Relative contributions of cystathionine beta-synthase and gamma-cystathionase to H2S biogenesis via alternative trans-sulfuration reactions. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19531479/ · DOI 10.1074/jbc.M109.010868
Complete structured claim and evidence
Cth-null mice on a low cyst(e)ine diet developed reduced liver/muscle glutathione, acute skeletal myopathy and fatal paralysis in the reported model.
Mouse Cth loss combined with low cyst(e)ine diet → Severe skeletal myopathy during mouse cysteine depletion source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse Cth deletion with controlled low cyst(e)ine feeding.
limitations
Genetic plus dietary intervention; this does not establish a dose threshold for healthy people.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
Diet became essential when the animal could not make enough internally.
primary_references
Cystathionine gamma-Lyase-deficient mice require dietary cysteine to protect against acute lethal myopathy and oxidative injury. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20566639/ · DOI 10.1074/jbc.M110.147439
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 300–306
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse Cth deletion with controlled low cyst(e)ine feeding. · source_derived_draft · unverified_draft
## l-cysteine-cth-diet-myopathy Diet became essential when the animal could not make enough internally. Cth-null mice on a low cyst(e)ine diet developed reduced liver/muscle glutathione, acute skeletal myopathy and fatal paralysis in the reported model. Model: Mouse Cth deletion with controlled low cyst(e)ine feeding. Limitations: Genetic plus dietary intervention; this does not establish a dose threshold for healthy people. Evidence access: Primary abstract Cystathionine gamma-Lyase-deficient mice require dietary cysteine to protect against acute lethal myopathy and oxidative injury. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20566639/ · DOI 10.1074/jbc.M110.147439
Complete structured claim and evidence
Combined Cse loss and cysteine-free feeding reduced liver and muscle CoA, alongside glutathione depletion and major metabolic changes.
Mouse Cth/Cse loss with cysteine-free diet → Tissue coenzyme A during mouse cysteine depletion source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Mouse genetic/dietary depletion; tissue CoA measurements at days 2 and 7.
limitations
CoA depletion accompanies several changes; do not assign all weight loss to one metabolite. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
A cysteine shortage reduced an energy-metabolism cofactor as well as an antioxidant.
primary_references
Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 308–314
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse genetic/dietary depletion; tissue CoA measurements at days 2 and 7. · source_derived_draft · unverified_draft
## l-cysteine-depletion-coa A cysteine shortage reduced an energy-metabolism cofactor as well as an antioxidant. Combined Cse loss and cysteine-free feeding reduced liver and muscle CoA, alongside glutathione depletion and major metabolic changes. Model: Mouse genetic/dietary depletion; tissue CoA measurements at days 2 and 7. Limitations: CoA depletion accompanies several changes; do not assign all weight loss to one metabolite. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8 Evidence access: Primary full text Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y
Complete structured claim and evidence
Cysteine-depleted Cse-null mice excreted more intermediary metabolites, including pyruvate, citrate, 2-oxoglutarate and orotate, with altered hepatic glycolytic and TCA-cycle metabolism.
Mouse Cth/Cse loss with cysteine-free diet → Urinary intermediary-metabolite loss in cysteine-depleted mice source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Mouse tissue/urine metabolomics during combined genetic and dietary depletion.
limitations
Metabolite abundance alone is not complete pathway flux or a human diagnostic signature. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
The shortage affected how efficiently the animal retained and used fuel.
primary_references
Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 316–322
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse tissue/urine metabolomics during combined genetic and dietary depletion. · source_derived_draft · unverified_draft
## l-cysteine-depletion-carbon-loss The shortage affected how efficiently the animal retained and used fuel. Cysteine-depleted Cse-null mice excreted more intermediary metabolites, including pyruvate, citrate, 2-oxoglutarate and orotate, with altered hepatic glycolytic and TCA-cycle metabolism. Model: Mouse tissue/urine metabolomics during combined genetic and dietary depletion. Limitations: Metabolite abundance alone is not complete pathway flux or a human diagnostic signature. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8 Evidence access: Primary full text Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y
Complete structured claim and evidence
After seven days of cysteine depletion, Cse-null mice repleted with cysteine but kept B5-deficient had persistently lower CoA and less weight recovery than mice receiving both nutrients, despite restored liver glutathione.
Pantothenate (vitamin B5) → Tissue coenzyme A during mouse cysteine depletion source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Mouse cysteine repletion with or without dietary B5; subsequent tissue GSH/CoA and weight measurements.
limitations
A direct cross-nutrient repletion experiment in mice; not an established human treatment protocol. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
Restoring one nutrient repaired one branch but left another branch short of its other substrate.
primary_references
Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 324–330
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse cysteine repletion with or without dietary B5; subsequent tissue GSH/CoA and weight measurements. · source_derived_draft · unverified_draft
## l-cysteine-b5-blocks-coa-recovery Restoring one nutrient repaired one branch but left another branch short of its other substrate. After seven days of cysteine depletion, Cse-null mice repleted with cysteine but kept B5-deficient had persistently lower CoA and less weight recovery than mice receiving both nutrients, despite restored liver glutathione. Model: Mouse cysteine repletion with or without dietary B5; subsequent tissue GSH/CoA and weight measurements. Limitations: A direct cross-nutrient repletion experiment in mice; not an established human treatment protocol. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8 Evidence access: Primary full text Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y
Complete structured claim and evidence
Adding B5 to drinking water after seven days on the cysteine-sufficient, B5-deficient recovery diet promptly rescued the weight-recovery difference.
Pantothenate (vitamin B5) → Weight recovery after mouse cysteine depletion source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Mouse sequential nutrient-depletion/repletion experiment.
limitations
The endpoint was recovery from induced wasting, not weight gain or energy improvement in healthy people. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
A second missing nutrient limited recovery after the first was restored.
primary_references
Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 332–338
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse sequential nutrient-depletion/repletion experiment. · source_derived_draft · unverified_draft
## l-cysteine-b5-restores-weight-recovery A second missing nutrient limited recovery after the first was restored. Adding B5 to drinking water after seven days on the cysteine-sufficient, B5-deficient recovery diet promptly rescued the weight-recovery difference. Model: Mouse sequential nutrient-depletion/repletion experiment. Limitations: The endpoint was recovery from induced wasting, not weight gain or energy improvement in healthy people. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8 Evidence access: Primary full text Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y
Complete structured claim and evidence
Fgf21 knockout attenuated weight loss in mice fed a diet lacking both methionine and cysteine.
Mouse fibroblast growth factor 21 / Fgf21 → Weight loss during systemic cysteine depletion in mice source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Fgf21-null versus control mice on no-methionine/no-cysteine diets; separate from the Cse-null cysteine-only experiment.
limitations
Do not silently replace the combined restriction with cysteine-only restriction. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
A stress hormone contributed under combined sulfur-amino-acid withdrawal.
primary_references
Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 340–346
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Fgf21-null versus control mice on no-methionine/no-cysteine diets; separate from the Cse-null cysteine-only experiment. · source_derived_draft · unverified_draft
## l-cysteine-fgf21-combined-restriction A stress hormone contributed under combined sulfur-amino-acid withdrawal. Fgf21 knockout attenuated weight loss in mice fed a diet lacking both methionine and cysteine. Model: Fgf21-null versus control mice on no-methionine/no-cysteine diets; separate from the Cse-null cysteine-only experiment. Limitations: Do not silently replace the combined restriction with cysteine-only restriction. Correction record: Author correction published 12 December 2025 (2026 issue), PMID 41388205, DOI 10.1038/s41586-025-09780-8: two incorrect day-3 muscle histology panels in Extended Data Fig. 2f,g duplicated day-7 panels and were replaced. The authors state that figure and paper conclusions were unaffected. This is a figure correction, not independent validation. https://www.nature.com/articles/s41586-025-09780-8 Evidence access: Primary full text Unravelling cysteine-deficiency-associated rapid weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40399674/ · DOI 10.1038/s41586-025-08996-y
Complete structured claim and evidence
Adipose metabolomics after caloric restriction showed reduced cysteine in the sampled human white adipose tissue.
Human CALERIE-II caloric restriction → Cysteine measured in human subcutaneous adipose tissue source_derived_draftungraded
Experimental context and source evidence
availability_state
biomarker_context Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Human CALERIE-II biopsy metabolomics during caloric restriction.
limitations
This did not isolate cysteine restriction or demonstrate that lowering cysteine caused human weight loss.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
A human tissue measurement motivated further animal experiments.
primary_references
Cysteine depletion triggers adipose tissue thermogenesis and weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40461845/ · DOI 10.1038/s42255-025-01297-8
trigger_kind
biomarker_context Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 348–354
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human CALERIE-II biopsy metabolomics during caloric restriction. · source_derived_draft · unverified_draft
## l-cysteine-human-adipose-marker A human tissue measurement motivated further animal experiments. Adipose metabolomics after caloric restriction showed reduced cysteine in the sampled human white adipose tissue. Model: Human CALERIE-II biopsy metabolomics during caloric restriction. Limitations: This did not isolate cysteine restriction or demonstrate that lowering cysteine caused human weight loss. Evidence access: Primary full text Cysteine depletion triggers adipose tissue thermogenesis and weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40461845/ · DOI 10.1038/s42255-025-01297-8
Complete structured claim and evidence
Whole-body Cth-null mice fed a cysteine-free diet developed rapid fat loss and adipose browning; restoring cysteine reversed the phenotype, whereas prolonged depletion could be lethal.
Whole-body Cth loss plus cysteine-free feeding → Weight loss during systemic cysteine depletion in mice source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Mouse genetic/dietary depletion and repletion; lean and obese models.
limitations
Severe induced deficiency is not evidence for a safe human weight-loss strategy.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
Loss of the nutrient caused systemic stress, not simply a desirable fat-burning switch.
primary_references
Cysteine depletion triggers adipose tissue thermogenesis and weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40461845/ · DOI 10.1038/s42255-025-01297-8
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 356–362
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse genetic/dietary depletion and repletion; lean and obese models. · source_derived_draft · unverified_draft
## l-cysteine-systemic-depletion-reversal Loss of the nutrient caused systemic stress, not simply a desirable fat-burning switch. Whole-body Cth-null mice fed a cysteine-free diet developed rapid fat loss and adipose browning; restoring cysteine reversed the phenotype, whereas prolonged depletion could be lethal. Model: Mouse genetic/dietary depletion and repletion; lean and obese models. Limitations: Severe induced deficiency is not evidence for a safe human weight-loss strategy. Evidence access: Primary full text Cysteine depletion triggers adipose tissue thermogenesis and weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40461845/ · DOI 10.1038/s42255-025-01297-8
Complete structured claim and evidence
Additional Fgf21 deletion in Cth-null mice did not prevent the rapid weight-loss phenotype during cysteine-free feeding.
Mouse fibroblast growth factor 21 / Fgf21 → Weight loss during systemic cysteine depletion in mice source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Cth-null versus Cth/Fgf21 double-null mice on cysteine-free diet for five days.
limitations
Different genotype and diet from the combined methionine/cysteine restriction study; no universal FGF21 dependence is assigned.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
An increased hormone level did not make that hormone necessary for this outcome.
primary_references
Cysteine depletion triggers adipose tissue thermogenesis and weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40461845/ · DOI 10.1038/s42255-025-01297-8
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 364–370
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Cth-null versus Cth/Fgf21 double-null mice on cysteine-free diet for five days. · source_derived_draft · unverified_draft
## l-cysteine-fgf21-cysteine-only-limit An increased hormone level did not make that hormone necessary for this outcome. Additional Fgf21 deletion in Cth-null mice did not prevent the rapid weight-loss phenotype during cysteine-free feeding. Model: Cth-null versus Cth/Fgf21 double-null mice on cysteine-free diet for five days. Limitations: Different genotype and diet from the combined methionine/cysteine restriction study; no universal FGF21 dependence is assigned. Evidence access: Primary full text Cysteine depletion triggers adipose tissue thermogenesis and weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40461845/ · DOI 10.1038/s42255-025-01297-8
Complete structured claim and evidence
The study linked cysteine-depletion-induced adipose browning and weight loss to sympathetic noradrenaline signaling through beta-3 adrenergic receptors.
Mouse beta-3 adrenergic receptor / Adrb3 → Weight loss during systemic cysteine depletion in mice source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Mouse systemic depletion with sympathetic and adrenergic perturbations.
limitations
Does not establish that cysteine directly binds the adrenergic receptor or that dietary changes reproduce the genetic model.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
The whole-body response involved nerve-to-fat signaling.
primary_references
Cysteine depletion triggers adipose tissue thermogenesis and weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40461845/ · DOI 10.1038/s42255-025-01297-8
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 372–378
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse systemic depletion with sympathetic and adrenergic perturbations. · source_derived_draft · unverified_draft
## l-cysteine-adrenergic-depletion-response The whole-body response involved nerve-to-fat signaling. The study linked cysteine-depletion-induced adipose browning and weight loss to sympathetic noradrenaline signaling through beta-3 adrenergic receptors. Model: Mouse systemic depletion with sympathetic and adrenergic perturbations. Limitations: Does not establish that cysteine directly binds the adrenergic receptor or that dietary changes reproduce the genetic model. Evidence access: Primary full text Cysteine depletion triggers adipose tissue thermogenesis and weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40461845/ · DOI 10.1038/s42255-025-01297-8
Complete structured claim and evidence
Cth/Ucp1 double-null mice still lost weight during cysteine deprivation; body-mass-adjusted energy expenditure was lower than in Cth-null mice in the reported comparison.
Mouse uncoupling protein 1 / Ucp1 → Weight loss during systemic cysteine depletion in mice source_derived_draftungraded
Experimental context and source evidence
availability_state
nutrient_deficiency Imported condition classification; unverified.
evidence_access
Primary full text
experimental_model
Mouse double-knockout comparisons, six-day diet and metabolic-cage analysis.
limitations
UCP1-independent weight loss must not be generalized to UCP1-independent heat production or identical energy expenditure.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
Persistence of weight loss does not mean every thermogenic measurement was unchanged.
primary_references
Cysteine depletion triggers adipose tissue thermogenesis and weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40461845/ · DOI 10.1038/s42255-025-01297-8
trigger_kind
nutrient_deficiency Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 380–386
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse double-knockout comparisons, six-day diet and metabolic-cage analysis. · source_derived_draft · unverified_draft
## l-cysteine-ucp1-endpoint-limit Persistence of weight loss does not mean every thermogenic measurement was unchanged. Cth/Ucp1 double-null mice still lost weight during cysteine deprivation; body-mass-adjusted energy expenditure was lower than in Cth-null mice in the reported comparison. Model: Mouse double-knockout comparisons, six-day diet and metabolic-cage analysis. Limitations: UCP1-independent weight loss must not be generalized to UCP1-independent heat production or identical energy expenditure. Evidence access: Primary full text Cysteine depletion triggers adipose tissue thermogenesis and weight loss. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40461845/ · DOI 10.1038/s42255-025-01297-8
Complete structured claim and evidence
The study reported direct EBF2 induction of Cars2 during brown-adipocyte differentiation.
Mouse early B-cell factor 2 / Ebf2 → Mouse mitochondrial cysteinyl-tRNA synthetase / Cars2 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse brown-fat study and cellular differentiation experiments.
limitations
Abstract-level extraction; detailed promoter occupancy and construct conditions require full-method review.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
A transcription factor increased the machinery for a sulfur-signaling pathway.
primary_references
Cars2-Mediated Cysteine Catabolism Drives Brown Fat Development and Thermogenesis Through Persulfidating EBF2. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41849685/ · DOI 10.1002/advs.202522690
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 388–394
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse brown-fat study and cellular differentiation experiments. · source_derived_draft · unverified_draft
## l-cysteine-ebf2-cars2-expression A transcription factor increased the machinery for a sulfur-signaling pathway. The study reported direct EBF2 induction of Cars2 during brown-adipocyte differentiation. Model: Mouse brown-fat study and cellular differentiation experiments. Limitations: Abstract-level extraction; detailed promoter occupancy and construct conditions require full-method review. Evidence access: Primary abstract Cars2-Mediated Cysteine Catabolism Drives Brown Fat Development and Thermogenesis Through Persulfidating EBF2. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41849685/ · DOI 10.1002/advs.202522690
Complete structured claim and evidence
Cars2-derived cysteine persulfide/H2S signaling promoted EBF2 persulfidation and interaction with PPARgamma or BRG1, supporting thermogenic gene recruitment.
Mouse mitochondrial cysteinyl-tRNA synthetase / Cars2 → Mouse early B-cell factor 2 / Ebf2 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse-centered brown-adipocyte and in vivo experimental program.
limitations
Abstract does not fully resolve each chemical intermediate; do not equate free H2S, CysSSH and protein-bound persulfides.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
Sulfur chemistry fed back to the transcription machinery.
primary_references
Cars2-Mediated Cysteine Catabolism Drives Brown Fat Development and Thermogenesis Through Persulfidating EBF2. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41849685/ · DOI 10.1002/advs.202522690
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 396–402
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse-centered brown-adipocyte and in vivo experimental program. · source_derived_draft · unverified_draft
## l-cysteine-cars2-ebf2-persulfidation Sulfur chemistry fed back to the transcription machinery. Cars2-derived cysteine persulfide/H2S signaling promoted EBF2 persulfidation and interaction with PPARgamma or BRG1, supporting thermogenic gene recruitment. Model: Mouse-centered brown-adipocyte and in vivo experimental program. Limitations: Abstract does not fully resolve each chemical intermediate; do not equate free H2S, CysSSH and protein-bound persulfides. Evidence access: Primary abstract Cars2-Mediated Cysteine Catabolism Drives Brown Fat Development and Thermogenesis Through Persulfidating EBF2. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41849685/ · DOI 10.1002/advs.202522690
Complete structured claim and evidence
Loss of Cars2 in thermogenic fat impaired brown-fat formation and reduced thermogenesis and energy expenditure in mice.
Mouse mitochondrial cysteinyl-tRNA synthetase / Cars2 → Brown-fat development and function in mouse Cars2 experiments source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_access
Primary abstract
experimental_model
Mouse thermogenic-fat Cars2 loss.
limitations
This is not the same intervention as Cth loss plus a cysteine-free diet.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
A tissue-specific enzyme defect produced a different response from whole-body nutrient withdrawal.
primary_references
Cars2-Mediated Cysteine Catabolism Drives Brown Fat Development and Thermogenesis Through Persulfidating EBF2. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41849685/ · DOI 10.1002/advs.202522690
trigger_kind
machinery_impairment Imported condition classification; unverified.
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 404–410
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse thermogenic-fat Cars2 loss. · source_derived_draft · unverified_draft
## l-cysteine-cars2-fat-loss A tissue-specific enzyme defect produced a different response from whole-body nutrient withdrawal. Loss of Cars2 in thermogenic fat impaired brown-fat formation and reduced thermogenesis and energy expenditure in mice. Model: Mouse thermogenic-fat Cars2 loss. Limitations: This is not the same intervention as Cth loss plus a cysteine-free diet. Evidence access: Primary abstract Cars2-Mediated Cysteine Catabolism Drives Brown Fat Development and Thermogenesis Through Persulfidating EBF2. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41849685/ · DOI 10.1002/advs.202522690
Complete structured claim and evidence
PLP treatment or an H2S donor improved brown-adipocyte function and reduced obesity progression in the reported high-fat-fed mouse experiments.
PLP → Brown-fat development and function in mouse Cars2 experiments source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Mouse high-fat-diet and brown-adipocyte experiments.
limitations
Abstract-only intervention details; no human dose, route equivalence or cysteine-plus-B6 synergy is established.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
A B6-derived coenzyme and a sulfur donor were separately tested inputs to this pathway.
primary_references
Cars2-Mediated Cysteine Catabolism Drives Brown Fat Development and Thermogenesis Through Persulfidating EBF2. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41849685/ · DOI 10.1002/advs.202522690
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 412–418
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse high-fat-diet and brown-adipocyte experiments. · source_derived_draft · unverified_draft
## l-cysteine-cars2-plp-intervention A B6-derived coenzyme and a sulfur donor were separately tested inputs to this pathway. PLP treatment or an H2S donor improved brown-adipocyte function and reduced obesity progression in the reported high-fat-fed mouse experiments. Model: Mouse high-fat-diet and brown-adipocyte experiments. Limitations: Abstract-only intervention details; no human dose, route equivalence or cysteine-plus-B6 synergy is established. Evidence access: Primary abstract Cars2-Mediated Cysteine Catabolism Drives Brown Fat Development and Thermogenesis Through Persulfidating EBF2. · 2026 · https://pubmed.ncbi.nlm.nih.gov/41849685/ · DOI 10.1002/advs.202522690
Complete structured claim and evidence
Human ADO oxidized exposed N-terminal cysteine residues in RGS4/5 peptides to the corresponding sulfinic-acid state using molecular oxygen.
Human 2-aminoethanethiol dioxygenase / ADO → Protein-incorporated N-terminal cysteine residue source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human ADO biochemistry, peptide substrates and human-cell experiments.
limitations
This is a protein-residue reaction, not evidence that ADO is the ordinary free-cysteine catabolic enzyme.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
A cysteine already built into a protein can serve as part of an oxygen-sensitive degradation signal.
primary_references
Conserved N-terminal cysteine dioxygenases transduce responses to hypoxia in animals and plants. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31273118/ · DOI 10.1126/science.aaw0112
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 420–426
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human ADO biochemistry, peptide substrates and human-cell experiments. · source_derived_draft · unverified_draft
## l-cysteine-ado-nterminal-oxidation A cysteine already built into a protein can serve as part of an oxygen-sensitive degradation signal. Human ADO oxidized exposed N-terminal cysteine residues in RGS4/5 peptides to the corresponding sulfinic-acid state using molecular oxygen. Model: Human ADO biochemistry, peptide substrates and human-cell experiments. Limitations: This is a protein-residue reaction, not evidence that ADO is the ordinary free-cysteine catabolic enzyme. Evidence access: Primary full text Conserved N-terminal cysteine dioxygenases transduce responses to hypoxia in animals and plants. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31273118/ · DOI 10.1126/science.aaw0112
Complete structured claim and evidence
ADO-dependent N-terminal cysteine oxidation regulated RGS4/5 stability through the N-degron pathway in human cells.
Human 2-aminoethanethiol dioxygenase / ADO → Human regulator of G-protein signaling 4 / RGS4 source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human-cell ADO and oxygen perturbations with N-degron readouts.
limitations
The downstream pathway requires additional machinery; dietary cysteine effects were not tested.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
Oxidation can mark a signaling regulator for degradation rather than merely damage it.
primary_references
Conserved N-terminal cysteine dioxygenases transduce responses to hypoxia in animals and plants. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31273118/ · DOI 10.1126/science.aaw0112
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 428–434
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human-cell ADO and oxygen perturbations with N-degron readouts. · source_derived_draft · unverified_draft
## l-cysteine-ado-protein-stability Oxidation can mark a signaling regulator for degradation rather than merely damage it. ADO-dependent N-terminal cysteine oxidation regulated RGS4/5 stability through the N-degron pathway in human cells. Model: Human-cell ADO and oxygen perturbations with N-degron readouts. Limitations: The downstream pathway requires additional machinery; dietary cysteine effects were not tested. Evidence access: Primary full text Conserved N-terminal cysteine dioxygenases transduce responses to hypoxia in animals and plants. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31273118/ · DOI 10.1126/science.aaw0112
Complete structured claim and evidence
Manipulating ADO altered G-protein-coupled calcium signals and MAP-kinase activity in the studied human cells.
Human 2-aminoethanethiol dioxygenase / ADO → G-protein-coupled calcium and MAPK signals in human ADO experiments source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text
experimental_model
Human-cell functional signaling assays.
limitations
Not evidence of dietary calcium or cysteine requirements for this response.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
Protein turnover connected an oxygen-sensing step to signaling outputs.
primary_references
Conserved N-terminal cysteine dioxygenases transduce responses to hypoxia in animals and plants. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31273118/ · DOI 10.1126/science.aaw0112
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 436–442
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human-cell functional signaling assays. · source_derived_draft · unverified_draft
## l-cysteine-ado-calcium-signals Protein turnover connected an oxygen-sensing step to signaling outputs. Manipulating ADO altered G-protein-coupled calcium signals and MAP-kinase activity in the studied human cells. Model: Human-cell functional signaling assays. Limitations: Not evidence of dietary calcium or cysteine requirements for this response. Evidence access: Primary full text Conserved N-terminal cysteine dioxygenases transduce responses to hypoxia in animals and plants. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31273118/ · DOI 10.1126/science.aaw0112
Complete structured claim and evidence
In eight healthy adults, adding 6.5 mg/kg/day cystine to a diet containing 5 mg/kg/day methionine did not significantly change methionine oxidation compared with the same low-methionine diet without cystine.
Cystine → Fed methionine oxidation in the 1997 cystine-intake study source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Six-day dietary periods followed by oral tracers and fasting/fed measurements on day seven.
limitations
This endpoint and regimen do not disprove every methionine-sparing effect or define current intake recommendations.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
A plausible nutrient-saving relationship was not detectable with this particular short-term measurement.
primary_references
Effect of cystine intake on methionine kinetics and oxidation determined with oral tracers of methionine and cysteine in healthy adults. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9250106/ · DOI 10.1093/ajcn/66.2.283
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 444–450
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Six-day dietary periods followed by oral tracers and fasting/fed measurements on day seven. · source_derived_draft · unverified_draft
## l-cysteine-methionine-sparing-limit A plausible nutrient-saving relationship was not detectable with this particular short-term measurement. In eight healthy adults, adding 6.5 mg/kg/day cystine to a diet containing 5 mg/kg/day methionine did not significantly change methionine oxidation compared with the same low-methionine diet without cystine. Model: Six-day dietary periods followed by oral tracers and fasting/fed measurements on day seven. Limitations: This endpoint and regimen do not disprove every methionine-sparing effect or define current intake recommendations. Evidence access: Primary abstract Effect of cystine intake on methionine kinetics and oxidation determined with oral tracers of methionine and cysteine in healthy adults. · 1997 · https://pubmed.ncbi.nlm.nih.gov/9250106/ · DOI 10.1093/ajcn/66.2.283
Complete structured claim and evidence
Human MPST transfers sulfur from 3-mercaptopyruvate to its active-site Cys248, releasing pyruvate and forming an enzyme-bound persulfide.
Human mercaptopyruvate sulfurtransferase / MPST → 3-Mercaptopyruvate source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract and primary figure descriptions
experimental_model
Purified human MPST structure and kinetics at pH 7.4.
limitations
The upstream cysteine transamination is pathway context; this experiment does not identify its dominant human tissue isoenzyme.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
A cysteine-derived intermediate hands sulfur to an enzyme before it reaches another acceptor.
primary_references
Structure and kinetic analysis of H2S production by human mercaptopyruvate sulfurtransferase. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23698001/ · DOI 10.1074/jbc.M113.466177
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 452–458
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human MPST structure and kinetics at pH 7.4. · source_derived_draft · unverified_draft
## l-cysteine-mpst-sulfur-transfer A cysteine-derived intermediate hands sulfur to an enzyme before it reaches another acceptor. Human MPST transfers sulfur from 3-mercaptopyruvate to its active-site Cys248, releasing pyruvate and forming an enzyme-bound persulfide. Model: Purified human MPST structure and kinetics at pH 7.4. Limitations: The upstream cysteine transamination is pathway context; this experiment does not identify its dominant human tissue isoenzyme. Evidence access: Primary abstract and primary figure descriptions Structure and kinetic analysis of H2S production by human mercaptopyruvate sulfurtransferase. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23698001/ · DOI 10.1074/jbc.M113.466177
Complete structured claim and evidence
Human MPST supported H2S production with thioredoxin and several low-molecular-weight acceptors, including cysteine, glutathione and dihydrolipoic acid.
Human mercaptopyruvate sulfurtransferase / MPST → Thiol acceptors in purified human MPST assays source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract and primary figure descriptions
experimental_model
Purified human MPST kinetics; concentrations and acceptors varied.
limitations
Some small-thiol assays used millimolar concentrations; these are not demonstrated effects of oral cysteine or lipoic acid.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
Sharing a sulfur-transfer route does not make these acceptors equally effective inside cells.
primary_references
Structure and kinetic analysis of H2S production by human mercaptopyruvate sulfurtransferase. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23698001/ · DOI 10.1074/jbc.M113.466177
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 460–466
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Purified human MPST kinetics; concentrations and acceptors varied. · source_derived_draft · unverified_draft
## l-cysteine-mpst-acceptor-choice Sharing a sulfur-transfer route does not make these acceptors equally effective inside cells. Human MPST supported H2S production with thioredoxin and several low-molecular-weight acceptors, including cysteine, glutathione and dihydrolipoic acid. Model: Purified human MPST kinetics; concentrations and acceptors varied. Limitations: Some small-thiol assays used millimolar concentrations; these are not demonstrated effects of oral cysteine or lipoic acid. Evidence access: Primary abstract and primary figure descriptions Structure and kinetic analysis of H2S production by human mercaptopyruvate sulfurtransferase. · 2013 · https://pubmed.ncbi.nlm.nih.gov/23698001/ · DOI 10.1074/jbc.M113.466177
Complete structured claim and evidence
Thioredoxin showed substrate inhibition in human MPST assays and increased the apparent Km for 3-mercaptopyruvate relative to other acceptors.
Thioredoxin / TXN → Human mercaptopyruvate sulfurtransferase / MPST source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Recombinant human MPST isoform kinetics.
limitations
Predicted tissue sulfur allocation was based on simulations; no human dietary response was measured.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
More of a redox partner did not simply produce a faster reaction.
primary_references
Thioredoxin regulates human mercaptopyruvate sulfurtransferase at physiologically-relevant concentrations. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32179647/ · DOI 10.1074/jbc.RA120.012616
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 468–474
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human MPST isoform kinetics. · source_derived_draft · unverified_draft
## l-cysteine-mpst-thioredoxin-inhibition More of a redox partner did not simply produce a faster reaction. Thioredoxin showed substrate inhibition in human MPST assays and increased the apparent Km for 3-mercaptopyruvate relative to other acceptors. Model: Recombinant human MPST isoform kinetics. Limitations: Predicted tissue sulfur allocation was based on simulations; no human dietary response was measured. Evidence access: Primary abstract Thioredoxin regulates human mercaptopyruvate sulfurtransferase at physiologically-relevant concentrations. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32179647/ · DOI 10.1074/jbc.RA120.012616
Complete structured claim and evidence
N-acetylcysteine was a poor MPST sulfur acceptor in the reported kinetic experiments.
N-Acetyl-L-cysteine → Human mercaptopyruvate sulfurtransferase / MPST source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Recombinant human MPST assays.
limitations
This does not negate NAC metabolism to cysteine or its other mechanisms.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
A cysteine precursor does not necessarily substitute for cysteine in each chemical reaction.
primary_references
Thioredoxin regulates human mercaptopyruvate sulfurtransferase at physiologically-relevant concentrations. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32179647/ · DOI 10.1074/jbc.RA120.012616
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 476–482
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human MPST assays. · source_derived_draft · unverified_draft
## l-cysteine-mpst-nac-distinction A cysteine precursor does not necessarily substitute for cysteine in each chemical reaction. N-acetylcysteine was a poor MPST sulfur acceptor in the reported kinetic experiments. Model: Recombinant human MPST assays. Limitations: This does not negate NAC metabolism to cysteine or its other mechanisms. Evidence access: Primary abstract Thioredoxin regulates human mercaptopyruvate sulfurtransferase at physiologically-relevant concentrations. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32179647/ · DOI 10.1074/jbc.RA120.012616
Complete structured claim and evidence
Human ERO1A targets PDI through contacts with its b-prime substrate-binding domain, supporting the disulfide-forming pathway for protein folding.
Human endoplasmic reticulum oxidoreductin 1 alpha / ERO1A → The prolyl 4-hydroxylase beta subunit, identical to protein disulfide isomerase source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human ERO1A structural and biochemical study.
limitations
Protein-residue oxidation is separate from free cystine reduction; dietary cysteine effects were not tested.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
Cysteines already incorporated into proteins are joined and rearranged during folding.
primary_references
Crystal structures of human Ero1α reveal the mechanisms of regulated and targeted oxidation of PDI. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20834232/ · DOI 10.1038/emboj.2010.222
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 484–490
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human ERO1A structural and biochemical study. · source_derived_draft · unverified_draft
## l-cysteine-ero1-pdi-targeting Cysteines already incorporated into proteins are joined and rearranged during folding. Human ERO1A targets PDI through contacts with its b-prime substrate-binding domain, supporting the disulfide-forming pathway for protein folding. Model: Human ERO1A structural and biochemical study. Limitations: Protein-residue oxidation is separate from free cystine reduction; dietary cysteine effects were not tested. Evidence access: Primary abstract Crystal structures of human Ero1α reveal the mechanisms of regulated and targeted oxidation of PDI. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20834232/ · DOI 10.1038/emboj.2010.222
Complete structured claim and evidence
Regulatory cysteines in a flexible ERO1A loop change disulfide arrangements and electron transfer, restraining its oxidative activity.
Regulatory cysteine residues in human ERO1A → Human endoplasmic reticulum oxidoreductin 1 alpha / ERO1A source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary abstract
experimental_model
Human ERO1A hyperactive and inactive crystal structures.
limitations
This is enzyme regulation, not proof that additional cysteine increases protein folding or antioxidant capacity.
nutrient_topic
L-Cysteine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Cysteine
plain_language
Cysteine bonds can regulate an enzyme as well as stabilize folded proteins.
primary_references
Crystal structures of human Ero1α reveal the mechanisms of regulated and targeted oxidation of PDI. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20834232/ · DOI 10.1038/emboj.2010.222
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19) · lines 492–498
AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human ERO1A hyperactive and inactive crystal structures. · source_derived_draft · unverified_draft
## l-cysteine-ero1-regulatory-disulfides Cysteine bonds can regulate an enzyme as well as stabilize folded proteins. Regulatory cysteines in a flexible ERO1A loop change disulfide arrangements and electron transfer, restraining its oxidative activity. Model: Human ERO1A hyperactive and inactive crystal structures. Limitations: This is enzyme regulation, not proof that additional cysteine increases protein folding or antioxidant capacity. Evidence access: Primary abstract Crystal structures of human Ero1α reveal the mechanisms of regulated and targeted oxidation of PDI. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20834232/ · DOI 10.1038/emboj.2010.222
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
PLP binds human CTH at Lys212 in an active site assembled from adjacent subunits.
PLP → Human cystathionine gamma-lyase / CTH source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
Second PLP-dependent step of sulfur amino-acid transsulfuration.
evidence_location
Apo, PLP and PLP-PAG structural comparisons
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
CTH needs an assembled B6-binding catalytic site.
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 541–552
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-plp PLP binds human CTH at Lys212 in an active site assembled from adjacent subunits. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: CTH needs an assembled B6-binding catalytic site. 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: Second PLP-dependent step of sulfur amino-acid transsulfuration. evidence_location: Apo, PLP and PLP-PAG structural comparisons [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
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
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
Recombinant human PPCS ligated L-cysteine to 4′-phosphopantothenate in a nucleotide-dependent reaction forming 4′-phosphopantothenoylcysteine.
Phosphopantothenoylcysteine synthetase / PPCS → 4-Phosphopantothenate source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution
exposure
Coupled PPCS assay: 1.5 mM phosphopantothenate, 5 mM cysteine and 1 mM ATP or CTP; 2 mM MgCl2, pH 8.0, 37°C.
limitations
Human enzyme expressed in E. coli; assay substrate supply is not evidence that oral cysteine raises human CoA or that low blood cysteine gates B5 repletion.
nutrient_topic
Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
organism
Homo sapiens
plain_language
Cysteine supplies the sulfur-containing portion of the developing CoA molecule.
primary_references
[b5-bio-daugherty2002] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 522–533
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution · source_derived_draft · unverified_draft
### b5-bio-ppcs-ligation Recombinant human PPCS ligated L-cysteine to 4′-phosphopantothenate in a nucleotide-dependent reaction forming 4′-phosphopantothenoylcysteine. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cysteine supplies the sulfur-containing portion of the developing CoA molecule. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution limitations: Human enzyme expressed in E. coli; assay substrate supply is not evidence that oral cysteine raises human CoA or that low blood cysteine gates B5 repletion. exposure: Coupled PPCS assay: 1.5 mM phosphopantothenate, 5 mM cysteine and 1 mM ATP or CTP; 2 mM MgCl2, pH 8.0, 37°C. cross_nutrient: true [b5-bio-daugherty2002] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200
Complete structured claim and evidence
Recombinant human PPCDC converted phosphopantothenoylcysteine to 4′-phosphopantetheine, verified by coupled enzyme assays and pathway reconstitution.
Phosphopantothenoylcysteine decarboxylase / PPCDC → 4′-Phosphopantothenoyl-L-cysteine source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution
exposure
Coupled assay used 50 micrograms/mL PPCDC with downstream COASY and 5 mM ATP; downstream ATP use is not assigned to PPCDC itself.
limitations
Coupled-assay confirmation and HPLC reconstitution; no dietary riboflavin depletion/repletion was tested.
nutrient_topic
Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
organism
Homo sapiens
plain_language
PPCDC removes the cysteine carboxyl group to produce the next CoA intermediate.
primary_references
[b5-bio-daugherty2002] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 548–559
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution · source_derived_draft · unverified_draft
### b5-bio-ppcdc-decarboxylation Recombinant human PPCDC converted phosphopantothenoylcysteine to 4′-phosphopantetheine, verified by coupled enzyme assays and pathway reconstitution. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: PPCDC removes the cysteine carboxyl group to produce the next CoA intermediate. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution limitations: Coupled-assay confirmation and HPLC reconstitution; no dietary riboflavin depletion/repletion was tested. exposure: Coupled assay used 50 micrograms/mL PPCDC with downstream COASY and 5 mM ATP; downstream ATP use is not assigned to PPCDC itself. cross_nutrient: true [b5-bio-daugherty2002] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200
Complete structured claim and evidence
Purified recombinant human PPCDC showed flavin-like absorbance maxima at 382 and 458 nm and approximately equimolar FMN association.
Phosphopantothenoylcysteine decarboxylase / PPCDC → Flavin mononucleotide source_derived_draftungraded
Experimental context and source evidence
cross_nutrient
true
experimental_model
Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution
exposure
Purified human recombinant protein spectroscopy and cofactor characterization.
limitations
Direct enzyme-cofactor evidence; the study did not test dietary B2 deficiency, oral riboflavin rescue, or a universal FMN threshold. FMN origin from B2 is shared nutrient context, not a newly demonstrated dietary effect.
nutrient_topic
Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
organism
Homo sapiens
plain_language
The CoA pathway contains a direct biochemical connection to the B2 cofactor FMN.
primary_references
[b5-bio-daugherty2002] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200
tissue_or_cell_type
Purified recombinant protein; no intact tissue
Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 561–572
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution · source_derived_draft · unverified_draft
### b5-bio-ppcdc-fmn Purified recombinant human PPCDC showed flavin-like absorbance maxima at 382 and 458 nm and approximately equimolar FMN association. Condition category: normal nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The CoA pathway contains a direct biochemical connection to the B2 cofactor FMN. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human PPCS, PPCDC and COASY expressed in Escherichia coli; coupled enzyme assays and HPLC reconstitution limitations: Direct enzyme-cofactor evidence; the study did not test dietary B2 deficiency, oral riboflavin rescue, or a universal FMN threshold. FMN origin from B2 is shared nutrient context, not a newly demonstrated dietary effect. exposure: Purified human recombinant protein spectroscopy and cofactor characterization. cross_nutrient: true [b5-bio-daugherty2002] Complete reconstitution of the human coenzyme A biosynthetic pathway via comparative genomics. (2002). https://pubmed.ncbi.nlm.nih.gov/11923312/ DOI: 10.1074/jbc.m201708200
Complete structured claim and evidence
Human NFS1 transferred sulfur from L-cysteine through an NFS1-bound persulfide intermediate to the rhodanese-like domain of MOCS3.
Human cysteine desulfurase / NFS1 → L-Cysteine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/molybdenum-research/18650437.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8180bd148722e8980ef5acbd4ae4c29a0d9d13da56bbccb91165a5eed4ab6f50", "start_char": 0, "end_char": 1547, "text_sha256": "8180bd148722e8980ef5acbd4ae4c29a0d9d13da56bbccb91165a5eed4ab6f50"}
experimental_model
Purified human NFS1/ISD11 and MOCS3 rhodanese-domain interaction and sulfur-transfer assays
exposure
L-cysteine sulfur-donor assays
limitations
Truncated and heterologously expressed proteins; cell localization was investigated independently in 2013.
nutrient_topic
Molybdenum research collection; topical membership is not evidence of a direct dietary effect. · Molybdenum
organism
Human proteins expressed in Escherichia coli
plain_language
Cysteine supplies sulfur that becomes part of the molybdenum cofactor.
primary_references
[mo-p18650437] A novel role for human Nfs1 in the cytoplasm: Nfs1 acts as a sulfur donor for MOCS3, a protein involved in molybdenum cofactor biosynthesis. (2008). https://pubmed.ncbi.nlm.nih.gov/18650437/ DOI: 10.1074/jbc.m804064200
tissue_or_cell_type
Purified proteins
Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 352–363
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human NFS1/ISD11 and MOCS3 rhodanese-domain interaction and sulfur-transfer assays · source_derived_draft · unverified_draft
### mo-nfs1-sulfur Human NFS1 transferred sulfur from L-cysteine through an NFS1-bound persulfide intermediate to the rhodanese-like domain of MOCS3. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cysteine supplies sulfur that becomes part of the molybdenum cofactor. organism: Human proteins expressed in Escherichia coli tissue_or_cell_type: Purified proteins experimental_model: Purified human NFS1/ISD11 and MOCS3 rhodanese-domain interaction and sulfur-transfer assays limitations: Truncated and heterologously expressed proteins; cell localization was investigated independently in 2013. exposure: L-cysteine sulfur-donor assays evidence_span: {"source_cache": "artifacts/molybdenum-research/18650437.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8180bd148722e8980ef5acbd4ae4c29a0d9d13da56bbccb91165a5eed4ab6f50", "start_char": 0, "end_char": 1547, "text_sha256": "8180bd148722e8980ef5acbd4ae4c29a0d9d13da56bbccb91165a5eed4ab6f50"} [mo-p18650437] A novel role for human Nfs1 in the cytoplasm: Nfs1 acts as a sulfur donor for MOCS3, a protein involved in molybdenum cofactor biosynthesis. (2008). https://pubmed.ncbi.nlm.nih.gov/18650437/ DOI: 10.1074/jbc.m804064200
Complete structured claim and evidence
The purified human MOCOS NifS-like domain bound PLP and exhibited cysteine desulfurase activity.
PLP → Human molybdenum cofactor sulfurase / MOCOS source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/molybdenum-research/34356852.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8bf3a09c4f88994cf8adc50faf391e62ac27e7572e59e6606147f2c689212d07", "start_char": 41304, "end_char": 42029, "text_sha256": "b9b02aae5eb537bdffc178ceaa33177cef6448738c19cb1a8477ad543f4e970c"}
experimental_model
Xanthinuria families with recombinant human MOCOS-domain assays and a plant XDH homolog assay
exposure
PLP quantification, cysteine desulfurase assays and Moco/MPT binding
limitations
Human XDH C150F was functionally modeled using Arabidopsis XDH1 C161S, not purified human C150F; MOCOS assays used isolated domains.
nutrient_topic
Molybdenum research collection; topical membership is not evidence of a direct dietary effect. · Molybdenum
organism
Human genetics and human MOCOS proteins; plant XDH variant experiment separately
plain_language
Vitamin B6 chemistry helps supply the sulfur used to activate these molybdenum enzymes.
primary_references
[mo-p34356852] Classical Xanthinuria in Nine Israeli Families and Two Isolated Cases from Germany: Molecular, Biochemical and Population Genetics Aspects. (2021). https://pubmed.ncbi.nlm.nih.gov/34356852/ DOI: 10.3390/biomedicines9070788
tissue_or_cell_type
Patient samples and purified domains
Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 534–545
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Xanthinuria families with recombinant human MOCOS-domain assays and a plant XDH homolog assay · source_derived_draft · unverified_draft
### mo-mocos-plp The purified human MOCOS NifS-like domain bound PLP and exhibited cysteine desulfurase activity. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin B6 chemistry helps supply the sulfur used to activate these molybdenum enzymes. organism: Human genetics and human MOCOS proteins; plant XDH variant experiment separately tissue_or_cell_type: Patient samples and purified domains experimental_model: Xanthinuria families with recombinant human MOCOS-domain assays and a plant XDH homolog assay limitations: Human XDH C150F was functionally modeled using Arabidopsis XDH1 C161S, not purified human C150F; MOCOS assays used isolated domains. exposure: PLP quantification, cysteine desulfurase assays and Moco/MPT binding evidence_span: {"source_cache": "artifacts/molybdenum-research/34356852.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "8bf3a09c4f88994cf8adc50faf391e62ac27e7572e59e6606147f2c689212d07", "start_char": 41304, "end_char": 42029, "text_sha256": "b9b02aae5eb537bdffc178ceaa33177cef6448738c19cb1a8477ad543f4e970c"} [mo-p34356852] Classical Xanthinuria in Nine Israeli Families and Two Isolated Cases from Germany: Molecular, Biochemical and Population Genetics Aspects. (2021). https://pubmed.ncbi.nlm.nih.gov/34356852/ DOI: 10.3390/biomedicines9070788
Complete structured claim and evidence
Human sulfite oxidase converts sulfite to sulfate in the terminal oxidative step of cysteine catabolism.
Human sulfite oxidase / SUOX → Sulfite / SO3(2-) source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/molybdenum-research/31127934.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0efd64e9cde371d0223d63607f5f6b76aada3a628c526f915d9b306c9bef7de", "start_char": 0, "end_char": 1649, "text_sha256": "d0efd64e9cde371d0223d63607f5f6b76aada3a628c526f915d9b306c9bef7de"}
experimental_model
Human SUOX Gly362Ser patient fibroblasts and recombinant enzyme maturation assays
exposure
G362S versus WT protein; Moco reconstitution and molybdate supplementation in culture
limitations
One genotype; in-vitro molybdate rescue is not demonstrated clinical treatment for all SUOX defects.
nutrient_topic
Molybdenum research collection; topical membership is not evidence of a direct dietary effect. · Molybdenum
organism
Homo sapiens
plain_language
SUOX clears sulfite by changing it into sulfate.
primary_references
[mo-p31127934] Impaired mitochondrial maturation of sulfite oxidase in a patient with severe sulfite oxidase deficiency. (2019). https://pubmed.ncbi.nlm.nih.gov/31127934/ DOI: 10.1093/hmg/ddz109
tissue_or_cell_type
Mitochondrial intermembrane space; patient fibroblasts
Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 586–597
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SUOX Gly362Ser patient fibroblasts and recombinant enzyme maturation assays · source_derived_draft · unverified_draft
### mo-suox-reaction Human sulfite oxidase converts sulfite to sulfate in the terminal oxidative step of cysteine catabolism. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: SUOX clears sulfite by changing it into sulfate. organism: Homo sapiens tissue_or_cell_type: Mitochondrial intermembrane space; patient fibroblasts experimental_model: Human SUOX Gly362Ser patient fibroblasts and recombinant enzyme maturation assays limitations: One genotype; in-vitro molybdate rescue is not demonstrated clinical treatment for all SUOX defects. exposure: G362S versus WT protein; Moco reconstitution and molybdate supplementation in culture evidence_span: {"source_cache": "artifacts/molybdenum-research/31127934.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0efd64e9cde371d0223d63607f5f6b76aada3a628c526f915d9b306c9bef7de", "start_char": 0, "end_char": 1649, "text_sha256": "d0efd64e9cde371d0223d63607f5f6b76aada3a628c526f915d9b306c9bef7de"} [mo-p31127934] Impaired mitochondrial maturation of sulfite oxidase in a patient with severe sulfite oxidase deficiency. (2019). https://pubmed.ncbi.nlm.nih.gov/31127934/ DOI: 10.1093/hmg/ddz109
Complete structured claim and evidence
Human CDO1 oxidizes cysteine to cysteine sulfinic acid using molecular oxygen and a non-heme iron center.
Human cysteine dioxygenase / CDO1 → L-Cysteine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/molybdenum-research/17135237.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3ccd6f2de98887d17d935999238a88d8901fe8a66bb9b48c9cbd5d179bf180d6", "start_char": 0, "end_char": 1343, "text_sha256": "3ccd6f2de98887d17d935999238a88d8901fe8a66bb9b48c9cbd5d179bf180d6"}
experimental_model
Purified human CDO1 crystallography, substrate binding, metal analysis and mutants
exposure
L-cysteine oxidation with molecular oxygen
limitations
The overall reaction and iron requirement are recorded; disputed detailed structural intermediates are not assigned as settled.
nutrient_topic
Molybdenum research collection; topical membership is not evidence of a direct dietary effect. · Molybdenum
organism
Homo sapiens
plain_language
Iron-dependent CDO1 starts an upstream sulfur-breakdown route.
primary_references
[mo-p17135237] An insight into the mechanism of human cysteine dioxygenase. Key roles of the thioether-bonded tyrosine-cysteine cofactor. (2007). https://pubmed.ncbi.nlm.nih.gov/17135237/ DOI: 10.1074/jbc.m609337200
tissue_or_cell_type
Recombinant human cysteine dioxygenase
Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 677–688
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human CDO1 crystallography, substrate binding, metal analysis and mutants · source_derived_draft · unverified_draft
### mo-cdo-csa Human CDO1 oxidizes cysteine to cysteine sulfinic acid using molecular oxygen and a non-heme iron center. Condition category: normal nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: Iron-dependent CDO1 starts an upstream sulfur-breakdown route. organism: Homo sapiens tissue_or_cell_type: Recombinant human cysteine dioxygenase experimental_model: Purified human CDO1 crystallography, substrate binding, metal analysis and mutants limitations: The overall reaction and iron requirement are recorded; disputed detailed structural intermediates are not assigned as settled. exposure: L-cysteine oxidation with molecular oxygen evidence_span: {"source_cache": "artifacts/molybdenum-research/17135237.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "3ccd6f2de98887d17d935999238a88d8901fe8a66bb9b48c9cbd5d179bf180d6", "start_char": 0, "end_char": 1343, "text_sha256": "3ccd6f2de98887d17d935999238a88d8901fe8a66bb9b48c9cbd5d179bf180d6"} [mo-p17135237] An insight into the mechanism of human cysteine dioxygenase. Key roles of the thioether-bonded tyrosine-cysteine cofactor. (2007). https://pubmed.ncbi.nlm.nih.gov/17135237/ DOI: 10.1074/jbc.m609337200
Complete structured claim and evidence
Purified human CSAD decarboxylated L-cysteine sulfinic acid to hypotaurine in PLP-containing enzyme assays.
Human cysteine sulfinic acid decarboxylase / CSAD → Hypotaurine source_derived_draftungraded
Experimental context and source evidence
evidence_access
Primary full text, introduction and enzyme-assay results
experimental_model
Recombinant human enzyme; substrate kinetics and circular-dichroism assays.
limitations
Hypotaurine still needs oxidation to become taurine; this is not a human supplementation experiment.
nutrient_topic
Taurine collection; molecular form, preparation, species, exposure and manipulation remain explicit. · Taurine
plain_language
Vitamin B6-dependent CSAD performs a step between cysteine and taurine.
primary_references
A Novel, Easy Assay Method for Human Cysteine Sulfinic Acid Decarboxylase. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34068845/ · DOI 10.3390/life11050438
Taurine: synthesis, transport, mitochondrial decoding and nutrient interactions (2026-09-19) · lines 33–39
AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Recombinant human enzyme; substrate kinetics and circular-dichroism assays. · source_derived_draft · unverified_draft
## taurine-csad-cysteinesulfinate Vitamin B6-dependent CSAD performs a step between cysteine and taurine. Purified human CSAD decarboxylated L-cysteine sulfinic acid to hypotaurine in PLP-containing enzyme assays. Model: Recombinant human enzyme; substrate kinetics and circular-dichroism assays. Limitations: Hypotaurine still needs oxidation to become taurine; this is not a human supplementation experiment. Evidence access: Primary full text, introduction and enzyme-assay results A Novel, Easy Assay Method for Human Cysteine Sulfinic Acid Decarboxylase. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34068845/ · DOI 10.3390/life11050438
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
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
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
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
Cell-derived DHLA reduced extracellular cystine to cysteine in the tested cultures.
Free dihydrolipoic acid / DHLA → Cystine source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/9288403.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6a14c857d89c580ffe8866d7e5f06658dcc806429ae3a4b8ad4bd096f664a2e2", "start_char": 0, "end_char": 1497, "text_sha256": "6a14c857d89c580ffe8866d7e5f06658dcc806429ae3a4b8ad4bd096f664a2e2"}
experimental_model
Cell-culture thiol transport and glutathione experiments
exposure
Lipoic acid/DHLA treatment and extracellular thiol measurements
limitations
Cell-type and extracellular-substrate dependence; no demonstration of general methylation-vitamin depletion.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human, rat and mouse cells as specified
plain_language
Reduced lipoic acid made a glutathione building block more available.
primary_references
[ala-p9288403] Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. (1997). https://pubmed.ncbi.nlm.nih.gov/9288403/ DOI: 10.1002/biof.5520060303
tissue_or_cell_type
Human lymphocytes, Jurkat cells and erythrocytes; rat C6 and mouse NB41A3 cells
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 793–804
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-culture thiol transport and glutathione experiments · source_derived_draft · unverified_draft
### ala-dhla-cystine-cysteine Cell-derived DHLA reduced extracellular cystine to cysteine in the tested cultures. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reduced lipoic acid made a glutathione building block more available. organism: Human, rat and mouse cells as specified tissue_or_cell_type: Human lymphocytes, Jurkat cells and erythrocytes; rat C6 and mouse NB41A3 cells experimental_model: Cell-culture thiol transport and glutathione experiments limitations: Cell-type and extracellular-substrate dependence; no demonstration of general methylation-vitamin depletion. exposure: Lipoic acid/DHLA treatment and extracellular thiol measurements evidence_span: {"source_cache": "artifacts/ala-research/9288403.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6a14c857d89c580ffe8866d7e5f06658dcc806429ae3a4b8ad4bd096f664a2e2", "start_char": 0, "end_char": 1497, "text_sha256": "6a14c857d89c580ffe8866d7e5f06658dcc806429ae3a4b8ad4bd096f664a2e2"} [ala-p9288403] Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. (1997). https://pubmed.ncbi.nlm.nih.gov/9288403/ DOI: 10.1002/biof.5520060303
Complete structured claim and evidence
Increased extracellular cysteine supported cellular uptake and glutathione synthesis, bypassing dependence on cystine transport in the studied cells.
Cellular cysteine uptake → Cellular reduced-glutathione pool source_derived_draftungraded
Experimental context and source evidence
evidence_span
{"source_cache": "artifacts/ala-research/9288403.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6a14c857d89c580ffe8866d7e5f06658dcc806429ae3a4b8ad4bd096f664a2e2", "start_char": 0, "end_char": 1497, "text_sha256": "6a14c857d89c580ffe8866d7e5f06658dcc806429ae3a4b8ad4bd096f664a2e2"}
experimental_model
Cell-culture thiol transport and glutathione experiments
exposure
Lipoic acid/DHLA treatment and extracellular thiol measurements
limitations
Cell-type and extracellular-substrate dependence; no demonstration of general methylation-vitamin depletion.
nutrient_topic
Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. · Lipoic acid
organism
Human, rat and mouse cells as specified
plain_language
The cells could import ready-to-use cysteine instead of relying on cystine uptake.
primary_references
[ala-p9288403] Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. (1997). https://pubmed.ncbi.nlm.nih.gov/9288403/ DOI: 10.1002/biof.5520060303
tissue_or_cell_type
Human lymphocytes, Jurkat cells and erythrocytes; rat C6 and mouse NB41A3 cells
Alpha-lipoic acid: cofactor assembly, redox signaling and nutrient interactions (2026-09-17) · lines 806–817
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell-culture thiol transport and glutathione experiments · source_derived_draft · unverified_draft
### ala-cysteine-gsh-route Increased extracellular cysteine supported cellular uptake and glutathione synthesis, bypassing dependence on cystine transport in the studied cells. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cells could import ready-to-use cysteine instead of relying on cystine uptake. organism: Human, rat and mouse cells as specified tissue_or_cell_type: Human lymphocytes, Jurkat cells and erythrocytes; rat C6 and mouse NB41A3 cells experimental_model: Cell-culture thiol transport and glutathione experiments limitations: Cell-type and extracellular-substrate dependence; no demonstration of general methylation-vitamin depletion. exposure: Lipoic acid/DHLA treatment and extracellular thiol measurements evidence_span: {"source_cache": "artifacts/ala-research/9288403.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "6a14c857d89c580ffe8866d7e5f06658dcc806429ae3a4b8ad4bd096f664a2e2", "start_char": 0, "end_char": 1497, "text_sha256": "6a14c857d89c580ffe8866d7e5f06658dcc806429ae3a4b8ad4bd096f664a2e2"} [ala-p9288403] Lipoic acid increases de novo synthesis of cellular glutathione by improving cystine utilization. (1997). https://pubmed.ncbi.nlm.nih.gov/9288403/ DOI: 10.1002/biof.5520060303
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
Sulfite reacted stoichiometrically with cystine to form SSC; reduced cysteine did not form SSC in the same assay.
Sulfite / SO3(2-) → S-Sulfocysteine source_derived_draftungraded
Experimental context and source evidence
availability_state
machinery_impairment Imported condition classification; unverified.
evidence_span
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experimental_model
Primary murine neurons, chemical reaction assays and tungstate-induced MoCD mice
exposure
SSC/sulfite exposure; receptor/calcium/calpain inhibition
limitations
Mechanistic model evidence. Mouse drug rescue does not establish human treatment efficacy; sulfite also has SSC-independent toxicity.
nutrient_topic
Molybdenum research collection; topical membership is not evidence of a direct dietary effect. · Molybdenum
organism
Mus musculus neurons and mice; chemical reaction assays
plain_language
The oxidized and reduced forms of cysteine behave differently.
primary_references
[mo-p29106383] S-sulfocysteine/NMDA receptor-dependent signaling underlies neurodegeneration in molybdenum cofactor deficiency. (2017). https://pubmed.ncbi.nlm.nih.gov/29106383/ DOI: 10.1172/jci89885
tissue_or_cell_type
Neuronal receptors, intracellular calcium and inhibitory synapses
trigger_kind
machinery_impairment Imported condition classification; unverified.
Molybdenum: cofactor assembly, sulfur metabolism and nutrient interactions (2026-09-17) · lines 1236–1247
AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Primary murine neurons, chemical reaction assays and tungstate-induced MoCD mice · source_derived_draft · unverified_draft
### mo-ssc-formation Sulfite reacted stoichiometrically with cystine to form SSC; reduced cysteine did not form SSC in the same assay. Condition category: machinery_impairment nutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect. plain_language: The oxidized and reduced forms of cysteine behave differently. organism: Mus musculus neurons and mice; chemical reaction assays tissue_or_cell_type: Neuronal receptors, intracellular calcium and inhibitory synapses experimental_model: Primary murine neurons, chemical reaction assays and tungstate-induced MoCD mice limitations: Mechanistic model evidence. Mouse drug rescue does not establish human treatment efficacy; sulfite also has SSC-independent toxicity. exposure: SSC/sulfite exposure; receptor/calcium/calpain inhibition evidence_span: {"source_cache": "artifacts/molybdenum-research/29106383.fulltext.txt", "locator": "Exact primary full-text span; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d7cfb311498ba2a88e3fc04be988dcffda740bbd1d93ada686cabf801861cf2a", "start_char": 14310, "end_char": 15490, "text_sha256": "9a181fcee8488d6f7513a0fa1759320721a8663e58658ef9344c1354716e3284"} [mo-p29106383] S-sulfocysteine/NMDA receptor-dependent signaling underlies neurodegeneration in molybdenum cofactor deficiency. (2017). https://pubmed.ncbi.nlm.nih.gov/29106383/ DOI: 10.1172/jci89885
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.

A lysosomal transport defect blocks recycling

Condition: machinery_impairment · Human CTNS substrate-binding residues are mutated.

Normal role: Cells acquire, synthesize and recycle cysteine, then distribute it among protein synthesis, antioxidant systems and sulfur-dependent metabolism.

Recorded consequence: Cystine transport is lost despite substrate being present.

Scope: Experimental species, cell type and exposure are retained in every linked record.

Imported cystine needs a functioning reduction pathway

Condition: machinery_impairment · TXNDC17/Txndc17 is removed in separate human-cell and mouse experiments.

Normal role: Cells acquire, synthesize and recycle cysteine, then distribute it among protein synthesis, antioxidant systems and sulfur-dependent metabolism.

Recorded consequence: Cystine utilization falls and transsulfuration/redox adaptation changes the response to stress.

Scope: Experimental species, cell type and exposure are retained in every linked record.

Neuronal precursor delivery affects antioxidant and zinc handling

Condition: machinery_impairment · Mouse neuronal Slc1a1 is absent.

Normal role: Cells acquire, synthesize and recycle cysteine, then distribute it among protein synthesis, antioxidant systems and sulfur-dependent metabolism.

Recorded consequence: Neuronal glutathione and labile zinc change; NAC and zinc chelation test distinct rescue routes.

Scope: Experimental species, cell type and exposure are retained in every linked record.

Cysteine scarcity activates an adaptive AMPK pathway

Condition: nutrient_deficiency · Human cells are cultured with restricted or absent cystine.

Normal role: Cells acquire, synthesize and recycle cysteine, then distribute it among protein synthesis, antioxidant systems and sulfur-dependent metabolism.

Recorded consequence: CARS helps recruit CaMKK2 to AMPK; blocking adaptation reduces survival.

Scope: Experimental species, cell type and exposure are retained in every linked record.

One mitochondrial enzyme supports translation and sulfur chemistry

Condition: machinery_impairment · Human CARS2 is disrupted and tested with mutant rescue.

Normal role: Cells acquire, synthesize and recycle cysteine, then distribute it among protein synthesis, antioxidant systems and sulfur-dependent metabolism.

Recorded consequence: Translation, persulfide production and mitochondrial morphology respond differently to function-selective mutants.

Scope: Experimental species, cell type and exposure are retained in every linked record.

Cystine withdrawal can cause lipid-peroxide cell death

Condition: nutrient_deficiency · Cystine is removed from human pancreatic cancer cultures.

Normal role: Cells acquire, synthesize and recycle cysteine, then distribute it among protein synthesis, antioxidant systems and sulfur-dependent metabolism.

Recorded consequence: Four of five tested cell lines show ferroptotic sensitivity.

Scope: Experimental species, cell type and exposure are retained in every linked record.

Glutathione and CoA are separate downstream defenses

Condition: machinery_impairment · Cystine import, GSH synthesis or pantothenate kinase is inhibited, or mouse Slc7a11 deleted.

Normal role: Cells acquire, synthesize and recycle cysteine, then distribute it among protein synthesis, antioxidant systems and sulfur-dependent metabolism.

Recorded consequence: Single and combined pathway blocks produce different ferroptotic responses; downstream rescue is model-specific.

Scope: Experimental species, cell type and exposure are retained in every linked record.

A missing glutathione precursor can mimic extracellular-glutamate injury

Condition: nutrient_deficiency · Cystine is reduced in neuronal hybrid-cell culture medium.

Normal role: Cells maintain separate metabolic, extracellular and transmitter glutamate pools through regulated transport, synthesis, recycling and utilization.

Recorded consequence: Glutathione falls and oxidative injury develops.

Scope: Species, tissue and experimental exposure remain explicit in each linked step.

Glucose loss changes the cost of cystine uptake

Condition: nutrient_deficiency · SLC7A11-high human cells are deprived of glucose while taking up cystine.

Normal role: Cells acquire, synthesize and recycle cysteine, then distribute it among protein synthesis, antioxidant systems and sulfur-dependent metabolism.

Recorded consequence: NADPH demand, disulfide accumulation and actin collapse create a vulnerability distinct from ferroptosis.

Scope: Experimental species, cell type and exposure are retained in every linked record.

Actin assembly changes sensitivity to disulfide stress

Condition: machinery_impairment · The WAVE regulatory complex is inactivated during disulfide-stress experiments.

Normal role: Cells acquire, synthesize and recycle cysteine, then distribute it among protein synthesis, antioxidant systems and sulfur-dependent metabolism.

Recorded consequence: Susceptibility to disulfidptosis falls in the tested models.

Scope: Experimental species, cell type and exposure are retained in every linked record.

Synthesis failure plus dietary deprivation causes systemic illness

Condition: nutrient_deficiency · Mice with Cth/Cse loss receive low-cyst(e)ine or cysteine-free diets in separate studies.

Normal role: Cells acquire, synthesize and recycle cysteine, then distribute it among protein synthesis, antioxidant systems and sulfur-dependent metabolism.

Recorded consequence: GSH/CoA depletion, altered fuel use, wasting and severe injury occur; hormonal and thermogenic endpoints differ.

Scope: Experimental species, cell type and exposure are retained in every linked record.

Removing methionine as well changes the experiment

Condition: nutrient_deficiency · Fgf21-null mice receive a diet lacking both methionine and cysteine.

Normal role: Cells acquire, synthesize and recycle cysteine, then distribute it among protein synthesis, antioxidant systems and sulfur-dependent metabolism.

Recorded consequence: FGF21 contributes to weight loss in this combined-restriction setting.

Scope: Experimental species, cell type and exposure are retained in every linked record.

A tissue cysteine measurement is not a causal dietary test

Condition: biomarker_context · Human adipose is sampled during caloric restriction.

Normal role: Cells acquire, synthesize and recycle cysteine, then distribute it among protein synthesis, antioxidant systems and sulfur-dependent metabolism.

Recorded consequence: Cysteine falls, but the human study does not isolate its causal contribution.

Scope: Experimental species, cell type and exposure are retained in every linked record.

Tissue-specific sulfur signaling supports brown fat

Condition: machinery_impairment · Cars2 is removed from mouse thermogenic adipose tissue.

Normal role: Cells acquire, synthesize and recycle cysteine, then distribute it among protein synthesis, antioxidant systems and sulfur-dependent metabolism.

Recorded consequence: Brown-fat development and energy expenditure decrease in this distinct genetic model.

Scope: Experimental species, cell type and exposure are retained in every linked record.

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.

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
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
L-Cysteine: sulfur allocation, redox supply and cross-nutrient mechanisms (2026-09-19)AI-assisted research curation; primary references, access levels and experimental limitations individually identified. 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
Pantothenic acid (vitamin B5): coenzyme A, 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
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
Taurine: synthesis, transport, mitochondrial decoding and nutrient interactions (2026-09-19)AI-assisted research curation; primary-abstract references and experimental limitations individually identified. 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

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.

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

L-Cysteine

The mechanisms

Human SLC7A9 and SLC3A1 form the b0,+AT–rBAT obligatory exchanger for cystine/cationic amino-acid influx coupled to neutral amino-acid efflux.

Human cystinosin structures and functional assays support proton-coupled cystine export from the lysosomal lumen toward the cytosol.

Mutating human cystinosin K273, K280, D305, W138, N166 or F142 abolished cystine transport in the reported assays.

D346N substitution abolished the pH-dependent conformational switch; the authors proposed D346 as a key protonation site controlling human cystinosin transitions.

The human CTNS N288K variant altered conformation and suppressed engagement with Ragulator–Rag, linking transporter state with a nutrient-signaling complex.

TXNDC17 knockout in human HEK293 cells markedly reduced intracellular cystine reduction; wild-type TRP14 re-expression restored activity whereas its active-site mutant did not.

The reconstituted TRP14 system used thioredoxin reductase 1 and NADPH to drive disulfide-reduction reactions.

TXNDC17 knockout shifted human-cell cysteine supply toward transsulfuration, as assessed using labeled methionine and downstream sulfur metabolites.

TRP14 removed cysteinyl mixed-disulfide modifications from human peroxiredoxin 2 and restored its peroxide-reducing activity in vitro.

Txndc17 knockout mice showed protection in the acute pancreatitis model, accompanied by Nrf2-pathway activation and increased transsulfuration.

Slc1a1-null mice had lower neuronal glutathione, increased oxidant susceptibility and age-dependent brain atrophy and behavioral changes.

N-acetylcysteine treatment reversed reduced neuronal glutathione and oxidant-related abnormalities in EAAC1-deficient mice.

EAAC1-null mice had increased vesicular/cytosolic hippocampal zinc and greater zinc redistribution and neuronal injury after transient cerebral ischemia.

NAC restored neuronal glutathione and normalized basal zinc levels in EAAC1-null mice; NAC or zinc chelation reduced ischemia-associated zinc movement, superoxide and neuronal death.

Cysteine scarcity promoted CARS association with AMPK gamma-2, whereas cysteine inhibited this association in the reported experiments.

Under cysteine-deficient conditions, CARS promoted AMPK association with CaMKK2 and CaMKK2-dependent AMPK phosphorylation.

Blocking AMPK activation increased cell death under cysteine-deficient conditions in the tested cultures.

CARS2 disruption reduced mitochondrial cysteinyl-tRNA synthetase function, assessed in part through mitochondrial MTCO1 expression; mutant rescue distinguished this from persulfide synthesis.

CARS2 disruption lowered cysteine-persulfide production in human cells, and wild-type or the C78/257D mutant restored it despite differing effects on translation.

CARS2-deficient human cells had fragmented or shrunken mitochondria; re-expression of wild-type or persulfide-competent C78/257D CARS2 improved morphology, unlike the tested persulfide-impaired lysine mutants.

Cystine starvation induced lipid oxidation and ferroptosis in four of five tested human PDAC cell lines.

Carbon-13 cystine tracing showed labeling of glutathione and CoA over the experiment, including CoA labeling over 24 hours.

System xc− inhibition lowered CoA and increased upstream pantothenate in the tested pancreatic cancer cells.

Buthionine sulfoximine lowered glutathione without inducing lipid oxidation or loss of viability under the tested PDAC conditions.

Pantothenate-kinase inhibition combined with BSO synergistically induced ferroptosis in the reported PDAC assays.

Adding CoA prevented ferroptosis induced by imidazole ketone erastin in the reported PDAC cell experiments.

Deleting Slc7a11 in established genetically engineered mouse PDAC induced tumor-selective ferroptosis and inhibited growth.

High SLC7A11-mediated cystine uptake increased reliance on glucose and the pentose phosphate pathway; glucose deprivation depleted NADPH and promoted intracellular disulfide accumulation.

Preventing cystine uptake or removing cystine relieved the disulfide stress associated with glucose deprivation in SLC7A11-high cells.

Glucose starvation of SLC7A11-high human cancer cells induced abnormal disulfide bonding in actin-cytoskeleton proteins, F-actin collapse and disulfidptosis, distinct from apoptosis and ferroptosis.

Inactivation of the WAVE regulatory complex suppressed disulfidptosis, whereas constitutive Rac activation promoted it in the studied cells.

Sulfur-35 cysteine supplied sulfur for newly assembled iron–sulfur clusters incorporated into aconitase and ferredoxins in isolated mouse neuronal-cell mitochondria.

Labeled NFS1-bound persulfide was an intermediate; its sulfur release required iron, GTP and NADH, whereas ATP was required for the overall assembly pathway but not this release step.

Purified human CBS favored H2S production through replacement of cysteine by homocysteine over the tested alternative cysteine reactions.

Kinetic simulations predicted that SAM-dependent activation changes the relative CBS contribution to H2S generation at specified substrate concentrations.

Cth-null mice on a low cyst(e)ine diet developed reduced liver/muscle glutathione, acute skeletal myopathy and fatal paralysis in the reported model.

Combined Cse loss and cysteine-free feeding reduced liver and muscle CoA, alongside glutathione depletion and major metabolic changes.

Cysteine-depleted Cse-null mice excreted more intermediary metabolites, including pyruvate, citrate, 2-oxoglutarate and orotate, with altered hepatic glycolytic and TCA-cycle metabolism.

After seven days of cysteine depletion, Cse-null mice repleted with cysteine but kept B5-deficient had persistently lower CoA and less weight recovery than mice receiving both nutrients, despite restored liver glutathione.

Adding B5 to drinking water after seven days on the cysteine-sufficient, B5-deficient recovery diet promptly rescued the weight-recovery difference.

Fgf21 knockout attenuated weight loss in mice fed a diet lacking both methionine and cysteine.

Adipose metabolomics after caloric restriction showed reduced cysteine in the sampled human white adipose tissue.

Whole-body Cth-null mice fed a cysteine-free diet developed rapid fat loss and adipose browning; restoring cysteine reversed the phenotype, whereas prolonged depletion could be lethal.

Additional Fgf21 deletion in Cth-null mice did not prevent the rapid weight-loss phenotype during cysteine-free feeding.

The study linked cysteine-depletion-induced adipose browning and weight loss to sympathetic noradrenaline signaling through beta-3 adrenergic receptors.

Cth/Ucp1 double-null mice still lost weight during cysteine deprivation; body-mass-adjusted energy expenditure was lower than in Cth-null mice in the reported comparison.

The study reported direct EBF2 induction of Cars2 during brown-adipocyte differentiation.

Cars2-derived cysteine persulfide/H2S signaling promoted EBF2 persulfidation and interaction with PPARgamma or BRG1, supporting thermogenic gene recruitment.

Loss of Cars2 in thermogenic fat impaired brown-fat formation and reduced thermogenesis and energy expenditure in mice.

PLP treatment or an H2S donor improved brown-adipocyte function and reduced obesity progression in the reported high-fat-fed mouse experiments.

Human ADO oxidized exposed N-terminal cysteine residues in RGS4/5 peptides to the corresponding sulfinic-acid state using molecular oxygen.

ADO-dependent N-terminal cysteine oxidation regulated RGS4/5 stability through the N-degron pathway in human cells.

Manipulating ADO altered G-protein-coupled calcium signals and MAP-kinase activity in the studied human cells.

In eight healthy adults, adding 6.5 mg/kg/day cystine to a diet containing 5 mg/kg/day methionine did not significantly change methionine oxidation compared with the same low-methionine diet without cystine.

Human MPST transfers sulfur from 3-mercaptopyruvate to its active-site Cys248, releasing pyruvate and forming an enzyme-bound persulfide.

Human MPST supported H2S production with thioredoxin and several low-molecular-weight acceptors, including cysteine, glutathione and dihydrolipoic acid.

Thioredoxin showed substrate inhibition in human MPST assays and increased the apparent Km for 3-mercaptopyruvate relative to other acceptors.

N-acetylcysteine was a poor MPST sulfur acceptor in the reported kinetic experiments.

Human ERO1A targets PDI through contacts with its b-prime substrate-binding domain, supporting the disulfide-forming pathway for protein folding.

Regulatory cysteines in a flexible ERO1A loop change disulfide arrangements and electron transfer, restraining its oxidative activity.

PLP-dependent human CBS condenses serine with homocysteine to produce cystathionine.

Human CTH cleaves cystathionine to cysteine, 2-oxobutanoate and ammonia in a PLP-dependent reaction.

PLP binds human CTH at Lys212 in an active site assembled from adjacent subunits.

Tracing in a cultured human hepatoma cell line estimated that transsulfuration supplied homocysteine-derived sulfur to approximately half of the intracellular glutathione pool.

Whole-body cysteine flux and fractional cystathionine synthesis were unchanged; transsulfuration-derived cysteine synthesis was below detection in this fasting protocol.

Recombinant human PPCS ligated L-cysteine to 4′-phosphopantothenate in a nucleotide-dependent reaction forming 4′-phosphopantothenoylcysteine.

Recombinant human PPCDC converted phosphopantothenoylcysteine to 4′-phosphopantetheine, verified by coupled enzyme assays and pathway reconstitution.

Purified recombinant human PPCDC showed flavin-like absorbance maxima at 382 and 458 nm and approximately equimolar FMN association.

Human NFS1 transferred sulfur from L-cysteine through an NFS1-bound persulfide intermediate to the rhodanese-like domain of MOCS3.

The purified human MOCOS NifS-like domain bound PLP and exhibited cysteine desulfurase activity.

Human sulfite oxidase converts sulfite to sulfate in the terminal oxidative step of cysteine catabolism.

Human CDO1 oxidizes cysteine to cysteine sulfinic acid using molecular oxygen and a non-heme iron center.

Purified human CSAD decarboxylated L-cysteine sulfinic acid to hypotaurine in PLP-containing enzyme assays.

Glutamate-cysteine ligase joins glutamate and cysteine to form gamma-glutamylcysteine in the first glutathione-synthesis step.

Human GSS joins gamma-glutamylcysteine and glycine in an ATP-dependent reaction to form glutathione.

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

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.