Component

Human indoleamine 2,3-dioxygenase 1 / IDO1

Context-specific entity; species, compartment and exposure are stated on each claim.

9 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 it acts on

  1. Human IDO1 F226A, F227A and R231A mutants retained substrate binding but lacked catalytic activity.

    Human indoleamine 2,3-dioxygenase 1 / IDO1 → N-Formyl-L-kynurenine source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Human enzyme site-directed mutagenesis.
    limitations
    Engineered mutants, not a characterized common dietary disorder.
    nutrient_topic
    Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan
    plain_language
    Binding the nutrient is not enough to process it.
    primary_references
    Crystal structure of human indoleamine 2,3-dioxygenase: catalytic mechanism of O2 incorporation by a heme-containing dioxygenase. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16477023/ · DOI 10.1073/pnas.0508996103
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 178–184

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human enzyme site-directed mutagenesis. · source_derived_draft · unverified_draft

    ## tryptophan-ido-binding-not-catalysis Binding the nutrient is not enough to process it. Human IDO1 F226A, F227A and R231A mutants retained substrate binding but lacked catalytic activity. Model: Human enzyme site-directed mutagenesis. Limitations: Engineered mutants, not a characterized common dietary disorder. Evidence access: Primary abstract Crystal structure of human indoleamine 2,3-dioxygenase: catalytic mechanism of O2 incorporation by a heme-containing dioxygenase. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16477023/ · DOI 10.1073/pnas.0508996103
    Complete structured claim and evidence

  2. Human IDO1 uses heme-bound oxygen to cleave the tryptophan indole ring, incorporating both oxygen atoms during N-formylkynurenine formation.

    Human indoleamine 2,3-dioxygenase 1 / IDO1 → N-Formyl-L-kynurenine source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human IDO1 structure and mutagenesis.
    limitations
    Catalytic heme dependence does not establish benefit from extra dietary iron.
    nutrient_topic
    Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan
    plain_language
    An immune-regulated enzyme opens a different route for tryptophan.
    primary_references
    Crystal structure of human indoleamine 2,3-dioxygenase: catalytic mechanism of O2 incorporation by a heme-containing dioxygenase. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16477023/ · DOI 10.1073/pnas.0508996103

    Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 170–176

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human IDO1 structure and mutagenesis. · source_derived_draft · unverified_draft

    ## tryptophan-ido-ring-cleavage An immune-regulated enzyme opens a different route for tryptophan. Human IDO1 uses heme-bound oxygen to cleave the tryptophan indole ring, incorporating both oxygen atoms during N-formylkynurenine formation. Model: Human IDO1 structure and mutagenesis. Limitations: Catalytic heme dependence does not establish benefit from extra dietary iron. Evidence access: Primary abstract Crystal structure of human indoleamine 2,3-dioxygenase: catalytic mechanism of O2 incorporation by a heme-containing dioxygenase. · 2006 · https://pubmed.ncbi.nlm.nih.gov/16477023/ · DOI 10.1073/pnas.0508996103
    Complete structured claim and evidence

  3. IFN-gamma/IDO-driven tryptophan depletion reduced S6K phosphorylation in human HeLa cells; tryptophan repletion restored the mTOR readout.

    Human indoleamine 2,3-dioxygenase 1 / IDO1 → Human mechanistic target of rapamycin kinase / MTOR source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    evidence_access
    Primary full text, Figure 2
    experimental_model
    Human HeLa cells, depleted media and amino-acid add-back.
    limitations
    S6K phosphorylation is a pathway readout, not direct tryptophan binding to MTOR.
    nutrient_topic
    Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan
    plain_language
    Local depletion reduced a growth signal as well as changing metabolite supply.
    primary_references
    IDO inhibits a tryptophan sufficiency signal that stimulates mTOR: A novel IDO effector pathway targeted by D-1-methyl-tryptophan. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23264892/ · DOI 10.4161/onci.21716
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 402–408

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human HeLa cells, depleted media and amino-acid add-back. · source_derived_draft · unverified_draft

    ## tryptophan-trp-mtor Local depletion reduced a growth signal as well as changing metabolite supply. IFN-gamma/IDO-driven tryptophan depletion reduced S6K phosphorylation in human HeLa cells; tryptophan repletion restored the mTOR readout. Model: Human HeLa cells, depleted media and amino-acid add-back. Limitations: S6K phosphorylation is a pathway readout, not direct tryptophan binding to MTOR. Evidence access: Primary full text, Figure 2 IDO inhibits a tryptophan sufficiency signal that stimulates mTOR: A novel IDO effector pathway targeted by D-1-methyl-tryptophan. · 2012 · https://pubmed.ncbi.nlm.nih.gov/23264892/ · DOI 10.4161/onci.21716
    Complete structured claim and evidence

What acts on it

  1. CD40 ligand increased IFN-gamma-driven tryptophan catabolism in human monocyte-derived macrophages.

    Human CD40 ligand / CD40LG → Human indoleamine 2,3-dioxygenase 1 / IDO1 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text, Figure 5
    experimental_model
    Human macrophage and activated-T-cell coculture.
    limitations
    Not evidence that systemic tryptophan intake determines every immune response.
    nutrient_topic
    Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan
    plain_language
    Two immune signals jointly increased local consumption.
    primary_references
    Inhibition of T cell proliferation by macrophage tryptophan catabolism. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10224276/ · DOI 10.1084/jem.189.9.1363

    Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 346–352

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human macrophage and activated-T-cell coculture. · source_derived_draft · unverified_draft

    ## tryptophan-cd40-ifng-ido Two immune signals jointly increased local consumption. CD40 ligand increased IFN-gamma-driven tryptophan catabolism in human monocyte-derived macrophages. Model: Human macrophage and activated-T-cell coculture. Limitations: Not evidence that systemic tryptophan intake determines every immune response. Evidence access: Primary full text, Figure 5 Inhibition of T cell proliferation by macrophage tryptophan catabolism. · 1999 · https://pubmed.ncbi.nlm.nih.gov/10224276/ · DOI 10.1084/jem.189.9.1363
    Complete structured claim and evidence

  2. IFN-gamma induced IDO activity and depleted almost all culture-medium tryptophan over two to three days in responsive human KB and WiDr cells.

    Human interferon gamma / IFNG → Human indoleamine 2,3-dioxygenase 1 / IDO1 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human cancer-cell cultures.
    limitations
    Other tested cell lines lacked this induced enzyme response; not a universal effect of every interferon exposure.
    nutrient_topic
    Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan
    plain_language
    An immune signal can locally consume the available amino acid.
    primary_references
    Induction of indoleamine 2,3-dioxygenase: a mechanism of the antitumor activity of interferon gamma. · 1988 · https://pubmed.ncbi.nlm.nih.gov/3124115/ · DOI 10.1073/pnas.85.4.1242

    Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 322–328

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell cultures. · source_derived_draft · unverified_draft

    ## tryptophan-ifng-ido-depletion An immune signal can locally consume the available amino acid. IFN-gamma induced IDO activity and depleted almost all culture-medium tryptophan over two to three days in responsive human KB and WiDr cells. Model: Human cancer-cell cultures. Limitations: Other tested cell lines lacked this induced enzyme response; not a universal effect of every interferon exposure. Evidence access: Primary abstract Induction of indoleamine 2,3-dioxygenase: a mechanism of the antitumor activity of interferon gamma. · 1988 · https://pubmed.ncbi.nlm.nih.gov/3124115/ · DOI 10.1073/pnas.85.4.1242
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. IDO1 inhibitors did not block IL4I1 in the study, leaving an alternative route to AHR activation.

    Human interleukin-4-induced protein 1 / IL4I1 → Human aryl hydrocarbon receptor / AHR source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Cancer-mechanism experiments.
    limitations
    An explanation proposed for clinical trial failure, not proof that IL4I1 caused failure in every patient.
    nutrient_topic
    Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan
    plain_language
    Blocking one enzyme does not necessarily close a parallel route.
    primary_references
    IL4I1 Is a Metabolic Immune Checkpoint that Activates the AHR and Promotes Tumor Progression. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32818467/ · DOI 10.1016/j.cell.2020.07.038

    Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 458–464

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Cancer-mechanism experiments. · source_derived_draft · unverified_draft

    ## tryptophan-ido-drug-bypass Blocking one enzyme does not necessarily close a parallel route. IDO1 inhibitors did not block IL4I1 in the study, leaving an alternative route to AHR activation. Model: Cancer-mechanism experiments. Limitations: An explanation proposed for clinical trial failure, not proof that IL4I1 caused failure in every patient. Evidence access: Primary abstract IL4I1 Is a Metabolic Immune Checkpoint that Activates the AHR and Promotes Tumor Progression. · 2020 · https://pubmed.ncbi.nlm.nih.gov/32818467/ · DOI 10.1016/j.cell.2020.07.038
    Complete structured claim and evidence

  2. Adding tryptophan reversed IFN-gamma-associated growth suppression in KB cells in a dose- and time-dependent manner.

    L-Tryptophan → Proliferation of human KB cells source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Human KB culture after IFN-gamma.
    limitations
    Not a recommendation to support tumor growth with supplementation.
    nutrient_topic
    Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan
    plain_language
    Replacement helped where deprivation was the limiting mechanism.
    primary_references
    Induction of indoleamine 2,3-dioxygenase: a mechanism of the antitumor activity of interferon gamma. · 1988 · https://pubmed.ncbi.nlm.nih.gov/3124115/ · DOI 10.1073/pnas.85.4.1242
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 330–336

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human KB culture after IFN-gamma. · source_derived_draft · unverified_draft

    ## tryptophan-kb-repletion Replacement helped where deprivation was the limiting mechanism. Adding tryptophan reversed IFN-gamma-associated growth suppression in KB cells in a dose- and time-dependent manner. Model: Human KB culture after IFN-gamma. Limitations: Not a recommendation to support tumor growth with supplementation. Evidence access: Primary abstract Induction of indoleamine 2,3-dioxygenase: a mechanism of the antitumor activity of interferon gamma. · 1988 · https://pubmed.ncbi.nlm.nih.gov/3124115/ · DOI 10.1073/pnas.85.4.1242
    Complete structured claim and evidence

  3. Under IFN-gamma/IDO1-associated tryptophan shortage, human cancer cells continued translation with WARS1-associated phenylalanine incorporation at tryptophan positions.

    Human cytosolic tryptophanyl-tRNA synthetase / WARS1 → Human cancer-cell tryptophan-to-phenylalanine translational substitution source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    evidence_access
    Primary abstract; primary correction full text reviewed
    experimental_model
    Human cancer-cell depletion, molecular assays and tumor proteomics.
    limitations
    Not a DNA mutation or a universal consequence of a low-tryptophan meal. Tumor proteomic filtering was clarified in a correction. Correction record: The 2022 author correction adds omitted funding acknowledgements and clarifies that the maximum-sample peptide filter was used in the intra-tumour analysis (Fig. 3f) but not for W>F substitutants in the tumour-specific analysis (Fig. 3a). Authors report similar biological conclusions with both strategies. This is a publication correction, not an opposing mechanism claim. https://www.nature.com/articles/s41586-022-05097-y
    nutrient_topic
    Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan
    plain_language
    Severe local shortage can change what a cancer cell puts into a protein.
    primary_references
    Tryptophan depletion results in tryptophan-to-phenylalanine substitutants. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35264796/ · DOI 10.1038/s41586-022-04499-2
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 122–128

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human cancer-cell depletion, molecular assays and tumor proteomics. · source_derived_draft · unverified_draft

    ## tryptophan-w-to-f-shortage Severe local shortage can change what a cancer cell puts into a protein. Under IFN-gamma/IDO1-associated tryptophan shortage, human cancer cells continued translation with WARS1-associated phenylalanine incorporation at tryptophan positions. Model: Human cancer-cell depletion, molecular assays and tumor proteomics. Limitations: Not a DNA mutation or a universal consequence of a low-tryptophan meal. Tumor proteomic filtering was clarified in a correction. Correction record: The 2022 author correction adds omitted funding acknowledgements and clarifies that the maximum-sample peptide filter was used in the intra-tumour analysis (Fig. 3f) but not for W>F substitutants in the tumour-specific analysis (Fig. 3a). Authors report similar biological conclusions with both strategies. This is a publication correction, not an opposing mechanism claim. https://www.nature.com/articles/s41586-022-05097-y Evidence access: Primary abstract; primary correction full text reviewed Tryptophan depletion results in tryptophan-to-phenylalanine substitutants. · 2022 · https://pubmed.ncbi.nlm.nih.gov/35264796/ · DOI 10.1038/s41586-022-04499-2
    Complete structured claim and evidence

  4. Added tryptophan did not reverse IFN-gamma growth suppression in WiDr cells despite induced tryptophan catabolism.

    L-Tryptophan → Proliferation of human WiDr cells source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Human WiDr culture.
    limitations
    This experimentally observed context difference is not a contradiction requiring a universal single explanation.
    nutrient_topic
    Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan
    plain_language
    Another cell type retained suppression after the nutrient was replaced.
    primary_references
    Induction of indoleamine 2,3-dioxygenase: a mechanism of the antitumor activity of interferon gamma. · 1988 · https://pubmed.ncbi.nlm.nih.gov/3124115/ · DOI 10.1073/pnas.85.4.1242
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 338–344

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human WiDr culture. · source_derived_draft · unverified_draft

    ## tryptophan-widr-repletion-fails Another cell type retained suppression after the nutrient was replaced. Added tryptophan did not reverse IFN-gamma growth suppression in WiDr cells despite induced tryptophan catabolism. Model: Human WiDr culture. Limitations: This experimentally observed context difference is not a contradiction requiring a universal single explanation. Evidence access: Primary abstract Induction of indoleamine 2,3-dioxygenase: a mechanism of the antitumor activity of interferon gamma. · 1988 · https://pubmed.ncbi.nlm.nih.gov/3124115/ · DOI 10.1073/pnas.85.4.1242
    Complete structured claim and evidence

In the sources

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

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