Component

Cellular reduced-glutathione pool

Cellular reduced-glutathione pool. Species, exposure and limitations are retained in each linked claim.

6 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What acts on it

  1. DIM lowered cellular GSH in the lung-cancer experiments.

    3,3'-Diindolylmethane / DIM → Cellular reduced-glutathione pool source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/dim-research/40100489.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0", "start_char": 0, "end_char": 1722, "text_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0"}
    experimental_model
    Cell perturbation and xenograft experiments
    exposure
    DIM; NRF2 overexpression and pharmacological rescue controls
    limitations
    Preclinical cancer context. Reduced defense here differs from Nrf2 induction in fibroblasts; neither result proves a universal antioxidant or prooxidant effect in people.
    nutrient_topic
    Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. · 3,3'-Diindolylmethane / DIM
    organism
    Human non-small-cell lung-cancer cells and mouse xenografts
    plain_language
    Glutathione availability changed in these cells, not as a demonstrated whole-body nutrient deficiency.
    primary_references
    [dim-p40100489] 3,3'-diindolylmethane induces ferroptosis and inhibits proliferation in non-small-cell lung cancer through the AHR/NRF2/GPX4 axis. (2025). https://pubmed.ncbi.nlm.nih.gov/40100489/ DOI: 10.1007/s12672-025-02096-z
    tissue_or_cell_type
    Ferroptosis and AHR/NRF2/GPX4

    Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17) · lines 1325–1336

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cell perturbation and xenograft experiments · source_derived_draft · unverified_draft

    ### dim-nsclc-gsh DIM lowered cellular GSH in the lung-cancer experiments. Condition category: normal nutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect. plain_language: Glutathione availability changed in these cells, not as a demonstrated whole-body nutrient deficiency. organism: Human non-small-cell lung-cancer cells and mouse xenografts tissue_or_cell_type: Ferroptosis and AHR/NRF2/GPX4 experimental_model: Cell perturbation and xenograft experiments limitations: Preclinical cancer context. Reduced defense here differs from Nrf2 induction in fibroblasts; neither result proves a universal antioxidant or prooxidant effect in people. exposure: DIM; NRF2 overexpression and pharmacological rescue controls evidence_span: {"source_cache": "artifacts/dim-research/40100489.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0", "start_char": 0, "end_char": 1722, "text_sha256": "99bc986298e026c4bd40745004936bab65af37a931084f75634b89505f5b95d0"} [dim-p40100489] 3,3'-diindolylmethane induces ferroptosis and inhibits proliferation in non-small-cell lung cancer through the AHR/NRF2/GPX4 axis. (2025). https://pubmed.ncbi.nlm.nih.gov/40100489/ DOI: 10.1007/s12672-025-02096-z
    Complete structured claim and evidence

  2. 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

  3. In peripheral blood lymphocytes, lipoic-acid treatment mainly restored a low-thiol subpopulation rather than raising all cells above physiological thiol levels.

    Lipoic acid → 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 response depended on the cells’ starting condition.
    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 819–830

    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-lymphocyte-thiol-subset In peripheral blood lymphocytes, lipoic-acid treatment mainly restored a low-thiol subpopulation rather than raising all cells above physiological thiol levels. Condition category: normal nutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: The response depended on the cells’ starting condition. 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

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

    SLC25A39-knockout mammalian cells → Cellular reduced-glutathione pool source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/glutathione-research/34707288.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5", "start_char": 0, "end_char": 1450, "text_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5"}
    experimental_model
    Organelle metabolomics, genetics and targeted synthesis rescue
    exposure
    SLC25A39 loss, A39/A40 double loss and targeted GshF
    limitations
    Mitochondrial versus total-cell pools differ; engineered synthesis rescue is not oral supplementation.
    nutrient_topic
    Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
    organism
    Mammalian cells; separate mouse erythropoiesis experiments
    plain_language
    A normal total-cell result could conceal a mitochondrial shortage.
    primary_references
    [glutathione-p34707288] SLC25A39 is necessary for mitochondrial glutathione import in mammalian cells. (2021). https://pubmed.ncbi.nlm.nih.gov/34707288/ DOI: 10.1038/s41586-021-04025-w
    tissue_or_cell_type
    Mitochondria
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 476–487

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Organelle metabolomics, genetics and targeted synthesis rescue · source_derived_draft · unverified_draft

    ### glutathione-a39-cellular-null Whole-cell GSH levels were not reduced by SLC25A39 loss. Condition category: machinery_impairment nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: A normal total-cell result could conceal a mitochondrial shortage. organism: Mammalian cells; separate mouse erythropoiesis experiments tissue_or_cell_type: Mitochondria experimental_model: Organelle metabolomics, genetics and targeted synthesis rescue limitations: Mitochondrial versus total-cell pools differ; engineered synthesis rescue is not oral supplementation. exposure: SLC25A39 loss, A39/A40 double loss and targeted GshF evidence_span: {"source_cache": "artifacts/glutathione-research/34707288.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5", "start_char": 0, "end_char": 1450, "text_sha256": "7e6a64f24da95b93d7440f3424bb8a611f3fc962a5dd6344f5d0e11671e0bba5"} [glutathione-p34707288] SLC25A39 is necessary for mitochondrial glutathione import in mammalian cells. (2021). https://pubmed.ncbi.nlm.nih.gov/34707288/ DOI: 10.1038/s41586-021-04025-w
    Complete structured claim and evidence

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

    Human glutathione-specific gamma-glutamylcyclotransferase CHAC1 → Cellular reduced-glutathione pool source_derived_draftungraded
    Experimental context and source evidence
    evidence_span
    {"source_cache": "artifacts/glutathione-research/25931127.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a561d11e802b38659805fe90dcab499bf0f434dbe91fa5510cf1eb4efb3460b1", "start_char": 0, "end_char": 1504, "text_sha256": "a561d11e802b38659805fe90dcab499bf0f434dbe91fa5510cf1eb4efb3460b1"}
    experimental_model
    Human promoter reporters, binding assays and overexpression
    exposure
    ER stress, ATF4 and CHAC1 expression
    limitations
    Cell experiments; CHAC1 induction is not a dietary GSH-deficiency diagnosis.
    nutrient_topic
    Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
    organism
    Human
    plain_language
    Low glutathione can reflect increased breakdown, not just poor supply.
    primary_references
    [glutathione-p25931127] Human CHAC1 Protein Degrades Glutathione, and mRNA Induction Is Regulated by the Transcription Factors ATF4 and ATF3 and a Bipartite ATF/CRE Regulatory Element. (2015). https://pubmed.ncbi.nlm.nih.gov/25931127/ DOI: 10.1074/jbc.m114.635144
    tissue_or_cell_type
    HEK293 and U2OS cells

    Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 580–591

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human promoter reporters, binding assays and overexpression · source_derived_draft · unverified_draft

    ### glutathione-chac1-gsh CHAC1 overexpression depleted GSH in HEK293 cells; a catalytic mutation alleviated that depletion. Condition category: normal nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low glutathione can reflect increased breakdown, not just poor supply. organism: Human tissue_or_cell_type: HEK293 and U2OS cells experimental_model: Human promoter reporters, binding assays and overexpression limitations: Cell experiments; CHAC1 induction is not a dietary GSH-deficiency diagnosis. exposure: ER stress, ATF4 and CHAC1 expression evidence_span: {"source_cache": "artifacts/glutathione-research/25931127.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "a561d11e802b38659805fe90dcab499bf0f434dbe91fa5510cf1eb4efb3460b1", "start_char": 0, "end_char": 1504, "text_sha256": "a561d11e802b38659805fe90dcab499bf0f434dbe91fa5510cf1eb4efb3460b1"} [glutathione-p25931127] Human CHAC1 Protein Degrades Glutathione, and mRNA Induction Is Regulated by the Transcription Factors ATF4 and ATF3 and a Bipartite ATF/CRE Regulatory Element. (2015). https://pubmed.ncbi.nlm.nih.gov/25931127/ DOI: 10.1074/jbc.m114.635144
    Complete structured claim and evidence

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

    Human GCLC Arg127Cys, Pro158Leu, His370Leu and Pro414Leu variants → Cellular reduced-glutathione pool source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_span
    {"source_cache": "artifacts/glutathione-research/21657237.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0ef7f04eacc64f48cee159ed630014f38163f2b848bf36b99c4d371786f55d7", "start_char": 0, "end_char": 1854, "text_sha256": "d0ef7f04eacc64f48cee159ed630014f38163f2b848bf36b99c4d371786f55d7"}
    experimental_model
    Human variants in recombinant assays, mouse fibroblasts and yeast complementation
    exposure
    Four clinical GCLC variants with or without GCLM
    limitations
    Expression-system rescue does not establish a clinical therapy; Pro158Leu retains near-wild-type isolated kinetics.
    nutrient_topic
    Glutathione research collection; topical membership is not evidence of a direct dietary effect. · GSH
    organism
    Human GCLC/GCLM; mouse and yeast hosts
    plain_language
    Supply can fail because the synthesis machinery is defective.
    primary_references
    [glutathione-p21657237] Enzymatic defects underlying hereditary glutamate cysteine ligase deficiency are mitigated by association of the catalytic and regulatory subunits. (2011). https://pubmed.ncbi.nlm.nih.gov/21657237/ DOI: 10.1021/bi200708w
    tissue_or_cell_type
    GCL activity and cellular GSH
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Glutathione: metabolism, signaling and nutrient connections (2026-09-17) · lines 385–396

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human variants in recombinant assays, mouse fibroblasts and yeast complementation · source_derived_draft · unverified_draft

    ### glutathione-gclc-mutant-gsh All four mutant GCLC transfectants had lower GSH than wild type in Gclc-null mouse fibroblasts; Pro414Leu was most impaired. Condition category: machinery_impairment nutrient_topic: Glutathione research collection; topical membership is not evidence of a direct dietary effect. plain_language: Supply can fail because the synthesis machinery is defective. organism: Human GCLC/GCLM; mouse and yeast hosts tissue_or_cell_type: GCL activity and cellular GSH experimental_model: Human variants in recombinant assays, mouse fibroblasts and yeast complementation limitations: Expression-system rescue does not establish a clinical therapy; Pro158Leu retains near-wild-type isolated kinetics. exposure: Four clinical GCLC variants with or without GCLM evidence_span: {"source_cache": "artifacts/glutathione-research/21657237.abstract.txt", "locator": "Primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "d0ef7f04eacc64f48cee159ed630014f38163f2b848bf36b99c4d371786f55d7", "start_char": 0, "end_char": 1854, "text_sha256": "d0ef7f04eacc64f48cee159ed630014f38163f2b848bf36b99c4d371786f55d7"} [glutathione-p21657237] Enzymatic defects underlying hereditary glutamate cysteine ligase deficiency are mitigated by association of the catalytic and regulatory subunits. (2011). https://pubmed.ncbi.nlm.nih.gov/21657237/ DOI: 10.1021/bi200708w
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

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