Component

L-Kynurenine

Tryptophan-derived substrate at a branch point in the kynurenine pathway.

10 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 tumor-cell TDO-derived kynurenine supported AHR-dependent survival and motility in the study.

    L-Kynurenine → Human aryl hydrocarbon receptor / AHR source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human tumor-cell experiments with human brain-tumor associations.
    limitations
    The chemical identity of the active ligand requires care: later work identified potent trace kynurenine condensation products.
    nutrient_topic
    Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan
    plain_language
    The catabolic route could feed a tumor-associated signal.
    primary_references
    An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21976023/ · DOI 10.1038/nature10491

    Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 426–432

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human tumor-cell experiments with human brain-tumor associations. · source_derived_draft · unverified_draft

    ## tryptophan-tdo-ahr The catabolic route could feed a tumor-associated signal. Human tumor-cell TDO-derived kynurenine supported AHR-dependent survival and motility in the study. Model: Human tumor-cell experiments with human brain-tumor associations. Limitations: The chemical identity of the active ligand requires care: later work identified potent trace kynurenine condensation products. Evidence access: Primary abstract An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21976023/ · DOI 10.1038/nature10491
    Complete structured claim and evidence

  2. Incubation or storage increased kynurenine-solution AHR potency by 100–1000-fold; isolated trace condensation products accounted for potent activity.

    L-Kynurenine → Kynurenine-derived trace extended aromatic condensation products / TEACOPs source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Chemical purification, synthesis and mouse-AHR reporter/ligand-pocket experiments.
    limitations
    Does not quantify TEACOP concentrations in human tumors or prove every kynurenine-associated effect is caused by these products.
    nutrient_topic
    Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan
    plain_language
    What forms from a metabolite in solution can matter more than the nominal starting compound.
    primary_references
    Trace derivatives of kynurenine potently activate the aryl hydrocarbon receptor (AHR). · 2018 · https://pubmed.ncbi.nlm.nih.gov/29279331/ · DOI 10.1074/jbc.RA117.000631

    Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 434–440

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Chemical purification, synthesis and mouse-AHR reporter/ligand-pocket experiments. · source_derived_draft · unverified_draft

    ## tryptophan-teacop-formation What forms from a metabolite in solution can matter more than the nominal starting compound. Incubation or storage increased kynurenine-solution AHR potency by 100–1000-fold; isolated trace condensation products accounted for potent activity. Model: Chemical purification, synthesis and mouse-AHR reporter/ligand-pocket experiments. Limitations: Does not quantify TEACOP concentrations in human tumors or prove every kynurenine-associated effect is caused by these products. Evidence access: Primary abstract Trace derivatives of kynurenine potently activate the aryl hydrocarbon receptor (AHR). · 2018 · https://pubmed.ncbi.nlm.nih.gov/29279331/ · DOI 10.1074/jbc.RA117.000631
    Complete structured claim and evidence

What acts on it

  1. Human KMO membrane assays measured kynurenine conversion to 3-hydroxykynurenine with NADPH; at 200 micromolar NADPH, kynurenine Km was 2 micromolar.

    Human kynurenine 3-monooxygenase / KMO → L-Kynurenine source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    B2-FAD and nicotinamide-containing NADPH support a branch upstream of de novo niacin synthesis.
    evidence_location
    Fig 2f and Methods: kinetic assays; interpret species separately
    experimental_model
    Human KMO in Sf9 membrane preparations; mass-spectrometry kinetics; separate P. fluorescens KMO crystallography.
    exposure
    Purified-enzyme assay
    limitations
    Human functional assays and bacterial structures are distinct evidence; this experiment did not test dietary B2 restriction or total NAD synthesis.
    nutrient_topic
    Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)
    organism
    Homo sapiens
    plain_language
    A flavin enzyme directs tryptophan-derived kynurenine into the hydroxylated branch.
    primary_references
    [hutchinson2017] Structural and mechanistic basis of differentiated inhibitors of the acute pancreatitis target kynurenine-3-monooxygenase. (2017). https://pubmed.ncbi.nlm.nih.gov/28604669/ DOI: 10.1038/ncomms15827
    tissue_or_cell_type
    Sf9 membrane fraction expressing human KMO

    Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1234–1246

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human KMO in Sf9 membrane preparations; mass-spectrometry kinetics; separate P. fluorescens KMO crystallography. · source_derived_draft · unverified_draft

    ### b2-kmo-kynurenine-hydroxylation Human KMO membrane assays measured kynurenine conversion to 3-hydroxykynurenine with NADPH; at 200 micromolar NADPH, kynurenine Km was 2 micromolar. Condition category: normal nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: A flavin enzyme directs tryptophan-derived kynurenine into the hydroxylated branch. organism: Homo sapiens tissue_or_cell_type: Sf9 membrane fraction expressing human KMO experimental_model: Human KMO in Sf9 membrane preparations; mass-spectrometry kinetics; separate P. fluorescens KMO crystallography. limitations: Human functional assays and bacterial structures are distinct evidence; this experiment did not test dietary B2 restriction or total NAD synthesis. exposure: Purified-enzyme assay cross_nutrient: B2-FAD and nicotinamide-containing NADPH support a branch upstream of de novo niacin synthesis. evidence_location: Fig 2f and Methods: kinetic assays; interpret species separately [hutchinson2017] Structural and mechanistic basis of differentiated inhibitors of the acute pancreatitis target kynurenine-3-monooxygenase. (2017). https://pubmed.ncbi.nlm.nih.gov/28604669/ DOI: 10.1038/ncomms15827
    Complete structured claim and evidence

  2. Recombinant mouse Afmid hydrolyzed N-formyl-L-kynurenine with a Km of 0.18–0.19 mM, matching native mouse cytosolic enzyme.

    Mouse arylformamidase / Afmid → L-Kynurenine source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Mouse liver enzyme expressed in E. coli.
    limitations
    This experiment is mouse enzyme evidence, not direct human AFMID validation.
    nutrient_topic
    Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan
    plain_language
    A second enzyme removes the formyl group to produce kynurenine.
    primary_references
    Cloning, expression, and catalytic triad of recombinant arylformamidase. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15935693/ · DOI 10.1016/j.pep.2005.04.013

    Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 186–192

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse liver enzyme expressed in E. coli. · source_derived_draft · unverified_draft

    ## tryptophan-afmid-hydrolysis A second enzyme removes the formyl group to produce kynurenine. Recombinant mouse Afmid hydrolyzed N-formyl-L-kynurenine with a Km of 0.18–0.19 mM, matching native mouse cytosolic enzyme. Model: Mouse liver enzyme expressed in E. coli. Limitations: This experiment is mouse enzyme evidence, not direct human AFMID validation. Evidence access: Primary abstract Cloning, expression, and catalytic triad of recombinant arylformamidase. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15935693/ · DOI 10.1016/j.pep.2005.04.013
    Complete structured claim and evidence

  3. S162A, D247A or H279A substitutions in mouse Afmid each removed more than 99% of measured enzyme activity.

    Mouse arylformamidase / Afmid → L-Kynurenine source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Recombinant mouse enzyme mutations.
    limitations
    Does not quantify human variant effects or prove a clinical repletion failure.
    nutrient_topic
    Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan
    plain_language
    One defective catalytic residue can block the next step despite available substrate.
    primary_references
    Cloning, expression, and catalytic triad of recombinant arylformamidase. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15935693/ · DOI 10.1016/j.pep.2005.04.013
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 194–200

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Recombinant mouse enzyme mutations. · source_derived_draft · unverified_draft

    ## tryptophan-afmid-triad One defective catalytic residue can block the next step despite available substrate. S162A, D247A or H279A substitutions in mouse Afmid each removed more than 99% of measured enzyme activity. Model: Recombinant mouse enzyme mutations. Limitations: Does not quantify human variant effects or prove a clinical repletion failure. Evidence access: Primary abstract Cloning, expression, and catalytic triad of recombinant arylformamidase. · 2005 · https://pubmed.ncbi.nlm.nih.gov/15935693/ · DOI 10.1016/j.pep.2005.04.013
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Human KAT-II transaminates kynurenine to an intermediate that leads to kynurenic acid.

    AADAT / KAT II → Kynurenic acid source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human enzyme structural study and catalytic characterization.
    limitations
    The enzyme performs transamination; it does not directly perform every subsequent chemical rearrangement.
    nutrient_topic
    Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan
    plain_language
    Kynurenine can be diverted into a neuroactive branch.
    primary_references
    Structure of the PLP-Form of the Human Kynurenine Aminotransferase II in a Novel Spacegroup at 1.83 Å Resolution. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27023527/ · DOI 10.3390/ijms17040446

    Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 210–216

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human enzyme structural study and catalytic characterization. · source_derived_draft · unverified_draft

    ## tryptophan-kat2-kyna Kynurenine can be diverted into a neuroactive branch. Human KAT-II transaminates kynurenine to an intermediate that leads to kynurenic acid. Model: Human enzyme structural study and catalytic characterization. Limitations: The enzyme performs transamination; it does not directly perform every subsequent chemical rearrangement. Evidence access: Primary abstract Structure of the PLP-Form of the Human Kynurenine Aminotransferase II in a Novel Spacegroup at 1.83 Å Resolution. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27023527/ · DOI 10.3390/ijms17040446
    Complete structured claim and evidence

  2. Human KAT-II/AADAT is a PLP-dependent homodimer; the structure shows a PLP–Lys263 aldimine at its catalytic site.

    AADAT / KAT II → PLP source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human KAT-II crystal structure at 1.83 angstrom resolution.
    limitations
    Cofactor dependence alone does not define clinical B6 requirements or benefit from excess B6.
    nutrient_topic
    Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan
    plain_language
    Vitamin B6 participates in a branch enzyme, not only the serotonin route.
    primary_references
    Structure of the PLP-Form of the Human Kynurenine Aminotransferase II in a Novel Spacegroup at 1.83 Å Resolution. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27023527/ · DOI 10.3390/ijms17040446

    Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 202–208

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Human KAT-II crystal structure at 1.83 angstrom resolution. · source_derived_draft · unverified_draft

    ## tryptophan-kat2-plp Vitamin B6 participates in a branch enzyme, not only the serotonin route. Human KAT-II/AADAT is a PLP-dependent homodimer; the structure shows a PLP–Lys263 aldimine at its catalytic site. Model: Human KAT-II crystal structure at 1.83 angstrom resolution. Limitations: Cofactor dependence alone does not define clinical B6 requirements or benefit from excess B6. Evidence access: Primary abstract Structure of the PLP-Form of the Human Kynurenine Aminotransferase II in a Novel Spacegroup at 1.83 Å Resolution. · 2016 · https://pubmed.ncbi.nlm.nih.gov/27023527/ · DOI 10.3390/ijms17040446
    Complete structured claim and evidence

  3. Muscle-specific PGC-1alpha1 transgenic mice resisted depression-like changes induced by chronic mild stress or kynurenine administration as peripheral kynurenine handling shifted.

    Mouse PGC-1alpha1 / Ppargc1a isoform 1 → Mouse stress/kynurenine-associated depression-like behavior source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Mouse genetic overexpression and behavioral challenges.
    limitations
    Not proof that this is the sole human exercise–mood mechanism or that kynurenic acid freely enters the brain.
    nutrient_topic
    Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan
    plain_language
    A peripheral metabolic change altered a brain-related behavioral response.
    primary_references
    Skeletal muscle PGC-1α1 modulates kynurenine metabolism and mediates resilience to stress-induced depression. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25259918/ · DOI 10.1016/j.cell.2014.07.051

    Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 618–624

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse genetic overexpression and behavioral challenges. · source_derived_draft · unverified_draft

    ## tryptophan-muscle-brain-context A peripheral metabolic change altered a brain-related behavioral response. Muscle-specific PGC-1alpha1 transgenic mice resisted depression-like changes induced by chronic mild stress or kynurenine administration as peripheral kynurenine handling shifted. Model: Mouse genetic overexpression and behavioral challenges. Limitations: Not proof that this is the sole human exercise–mood mechanism or that kynurenic acid freely enters the brain. Evidence access: Primary abstract Skeletal muscle PGC-1α1 modulates kynurenine metabolism and mediates resilience to stress-induced depression. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25259918/ · DOI 10.1016/j.cell.2014.07.051
    Complete structured claim and evidence

  4. Carbidopa inhibition of kynurenine aminotransferase activity impaired aspartate synthesis and mitochondrial respiration and reduced mouse exercise performance and muscle force.

    Mouse skeletal-muscle kynurenine aminotransferases; multiple enzymes → Mouse muscle aspartate synthesis and mitochondrial respiration during kynurenine metabolism source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Mouse muscle/exercise experiments within a PGC-1alpha1 and malate–aspartate-shuttle study.
    limitations
    Carbidopa is not specific to a single KAT isoform; mouse exposures do not establish the same effect at a clinical human dose.
    nutrient_topic
    Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan
    plain_language
    The branch can support muscle energy handling as well as alter circulating metabolites.
    primary_references
    Skeletal muscle PGC-1α1 reroutes kynurenine metabolism to increase energy efficiency and fatigue-resistance. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31235694/ · DOI 10.1038/s41467-019-10712-0
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 626–632

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse muscle/exercise experiments within a PGC-1alpha1 and malate–aspartate-shuttle study. · source_derived_draft · unverified_draft

    ## tryptophan-muscle-kat-inhibition The branch can support muscle energy handling as well as alter circulating metabolites. Carbidopa inhibition of kynurenine aminotransferase activity impaired aspartate synthesis and mitochondrial respiration and reduced mouse exercise performance and muscle force. Model: Mouse muscle/exercise experiments within a PGC-1alpha1 and malate–aspartate-shuttle study. Limitations: Carbidopa is not specific to a single KAT isoform; mouse exposures do not establish the same effect at a clinical human dose. Evidence access: Primary abstract Skeletal muscle PGC-1α1 reroutes kynurenine metabolism to increase energy efficiency and fatigue-resistance. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31235694/ · DOI 10.1038/s41467-019-10712-0
    Complete structured claim and evidence

  5. The PGC-1alpha1–PPAR-alpha/delta program increased muscle kynurenine aminotransferases and conversion of kynurenine to kynurenic acid.

    Mouse PGC-1alpha1 / Ppargc1a isoform 1 → Mouse skeletal-muscle kynurenine aminotransferases; multiple enzymes source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Mouse skeletal-muscle transgenic and stress experiments.
    limitations
    Multiple aminotransferases are involved; do not assign the entire effect to human AADAT alone.
    nutrient_topic
    Tryptophan collection; molecular form, preparation, species, exposure and manipulation remain explicit. · L-Tryptophan
    plain_language
    Muscle metabolism can change which tryptophan products remain in circulation.
    primary_references
    Skeletal muscle PGC-1α1 modulates kynurenine metabolism and mediates resilience to stress-induced depression. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25259918/ · DOI 10.1016/j.cell.2014.07.051

    Tryptophan: transport, protein synthesis, neuroactive metabolites, NAD and microbial pathways (2026-09-19) · lines 610–616

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Mouse skeletal-muscle transgenic and stress experiments. · source_derived_draft · unverified_draft

    ## tryptophan-muscle-kat-program Muscle metabolism can change which tryptophan products remain in circulation. The PGC-1alpha1–PPAR-alpha/delta program increased muscle kynurenine aminotransferases and conversion of kynurenine to kynurenic acid. Model: Mouse skeletal-muscle transgenic and stress experiments. Limitations: Multiple aminotransferases are involved; do not assign the entire effect to human AADAT alone. Evidence access: Primary abstract Skeletal muscle PGC-1α1 modulates kynurenine metabolism and mediates resilience to stress-induced depression. · 2014 · https://pubmed.ncbi.nlm.nih.gov/25259918/ · DOI 10.1016/j.cell.2014.07.051
    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.

    Evidence, AI assistance and curation standards