Component

Homogentisate

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

4 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. Human HGD catalyzes aromatic-ring cleavage during phenylalanine/tyrosine degradation; its structure contains a coordinated active-site iron ion.

    Human homogentisate 1,2-dioxygenase / HGD → Homogentisate source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human apo and iron-bound HGD crystallography.
    limitations
    The study is structural/enzymatic evidence, not a trial of iron supplementation.
    nutrient_topic
    L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
    plain_language
    Iron-dependent chemistry opens the aromatic ring for further breakdown.
    primary_references
    Crystal structure of human homogentisate dioxygenase. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10876237/ · DOI 10.1038/76756

    L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism 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 apo and iron-bound HGD crystallography. · source_derived_draft · unverified_draft

    ## l-tyrosine-hgd-ring Iron-dependent chemistry opens the aromatic ring for further breakdown. Human HGD catalyzes aromatic-ring cleavage during phenylalanine/tyrosine degradation; its structure contains a coordinated active-site iron ion. Model: Human apo and iron-bound HGD crystallography. Limitations: The study is structural/enzymatic evidence, not a trial of iron supplementation. Evidence access: Primary abstract Crystal structure of human homogentisate dioxygenase. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10876237/ · DOI 10.1038/76756
    Complete structured claim and evidence

  2. Human HPD converts 4-hydroxyphenylpyruvate to homogentisate; substrate-binding-site mutations altered catalytic efficiency.

    Human 4-hydroxyphenylpyruvate dioxygenase / HPD → Homogentisate source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human enzyme mutagenesis, binding assays and structural simulation.
    limitations
    HPD must not be merged with HPDL, which has a different product.
    nutrient_topic
    L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
    plain_language
    The carbon skeleton passes through a separate oxygen-dependent enzyme.
    primary_references
    Functional role of residues involved in substrate binding of human 4-hydroxyphenylpyruvate dioxygenase. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34047349/ · DOI 10.1042/BCJ20210005

    L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism 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 · Human enzyme mutagenesis, binding assays and structural simulation. · source_derived_draft · unverified_draft

    ## l-tyrosine-hpd-hga The carbon skeleton passes through a separate oxygen-dependent enzyme. Human HPD converts 4-hydroxyphenylpyruvate to homogentisate; substrate-binding-site mutations altered catalytic efficiency. Model: Human enzyme mutagenesis, binding assays and structural simulation. Limitations: HPD must not be merged with HPDL, which has a different product. Evidence access: Primary abstract Functional role of residues involved in substrate binding of human 4-hydroxyphenylpyruvate dioxygenase. · 2021 · https://pubmed.ncbi.nlm.nih.gov/34047349/ · DOI 10.1042/BCJ20210005
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Alkaptonuria-associated HGD missense variants were concentrated in intersubunit contact regions of the human enzyme structure.

    Human homogentisate 1,2-dioxygenase / HGD → Human HGD-dependent homogentisate catabolism source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Mapping disease-associated variants onto a human hexameric structure.
    limitations
    Structural mapping is not a functional assay for every variant or a universal severity predictor.
    nutrient_topic
    L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
    plain_language
    How enzyme subunits fit together can affect metabolic disposal.
    primary_references
    Crystal structure of human homogentisate dioxygenase. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10876237/ · DOI 10.1038/76756
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism 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 · Mapping disease-associated variants onto a human hexameric structure. · source_derived_draft · unverified_draft

    ## l-tyrosine-hgd-variants How enzyme subunits fit together can affect metabolic disposal. Alkaptonuria-associated HGD missense variants were concentrated in intersubunit contact regions of the human enzyme structure. Model: Mapping disease-associated variants onto a human hexameric structure. Limitations: Structural mapping is not a functional assay for every variant or a universal severity predictor. Evidence access: Primary abstract Crystal structure of human homogentisate dioxygenase. · 2000 · https://pubmed.ncbi.nlm.nih.gov/10876237/ · DOI 10.1038/76756
    Complete structured claim and evidence

  2. During nitisinone treatment in SONIA 2, urinary derivatives upstream of homogentisate increased and tracked treatment-associated hypertyrosinemia.

    Nitisinone → Human alkaptonuria alternative urinary tyrosine metabolites source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    biomarker_context Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    AKU trial samples at baseline, 24 and 48 months; 47 treated serum and 53 treated urine sample series, with untreated comparisons.
    limitations
    Metabolite associations do not identify every conjugating enzyme or prove the proposed clearance benefit. This exposure is pharmacological.
    nutrient_topic
    L-Tyrosine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Tyrosine
    plain_language
    Blocking one step changes the distribution of metabolites across other routes.
    primary_references
    Comprehensive Biotransformation Analysis of Phenylalanine-Tyrosine Metabolism Reveals Alternative Routes of Metabolite Clearance in Nitisinone-Treated Alkaptonuria. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36295829/ · DOI 10.3390/metabo12100927
    trigger_kind
    biomarker_context Imported condition classification; unverified.

    L-Tyrosine: catecholamines, thyroid chemistry, pigment, metabolism 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 · AKU trial samples at baseline, 24 and 48 months; 47 treated serum and 53 treated urine sample series, with untreated comparisons. · source_derived_draft · unverified_draft

    ## l-tyrosine-nitisinone-network Blocking one step changes the distribution of metabolites across other routes. During nitisinone treatment in SONIA 2, urinary derivatives upstream of homogentisate increased and tracked treatment-associated hypertyrosinemia. Model: AKU trial samples at baseline, 24 and 48 months; 47 treated serum and 53 treated urine sample series, with untreated comparisons. Limitations: Metabolite associations do not identify every conjugating enzyme or prove the proposed clearance benefit. This exposure is pharmacological. Evidence access: Primary abstract Comprehensive Biotransformation Analysis of Phenylalanine-Tyrosine Metabolism Reveals Alternative Routes of Metabolite Clearance in Nitisinone-Treated Alkaptonuria. · 2022 · https://pubmed.ncbi.nlm.nih.gov/36295829/ · DOI 10.3390/metabo12100927
    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