Component

2-Oxoadipate

Independent small molecule record; interpretation is limited by each linked claim and its study context.

7 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. DHTKD1 with DLST and DLD supports oxidative decarboxylation of 2-oxoadipate to glutaryl-CoA, with NADH and carbon dioxide formation.

    2-Oxoadipate → Glutaryl-CoA source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Recombinant human DHTKD1 and DLST; structural and biochemical assays; Two human patients; fibroblast isotope tracing and genetic complementation
    limitations
    DHTKD1 is the E1 component, not a stand-alone enzyme performing every complex reaction.
    organism
    Homo sapiens
    plain_language
    A three-enzyme complex converts the carbon skeleton into glutaryl-CoA.
    primary_references
    [bezerra2020] Crystal structure and interaction studies of human DHTKD1 provide insight into a mitochondrial megacomplex in lysine catabolism (2020). https://pmc.ncbi.nlm.nih.gov/articles/PMC7340257/ DOI: 10.1107/S205225252000696X [danhauser2012] DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3516599/ DOI: 10.1016/j.ajhg.2012.10.006
    tissue_or_cell_type
    Mitochondrial matrix

    L-Lysine: mechanism-first literature curation (2026-09-17) · lines 125–134

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human DHTKD1 and DLST; structural and biochemical assays; Two human patients; fibroblast isotope tracing and genetic complementation · source_derived_draft · unverified_draft

    ### oxoadipate-dehydrogenase-complex DHTKD1 with DLST and DLD supports oxidative decarboxylation of 2-oxoadipate to glutaryl-CoA, with NADH and carbon dioxide formation. Plain language: A three-enzyme complex converts the carbon skeleton into glutaryl-CoA. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial matrix experimental_model: Recombinant human DHTKD1 and DLST; structural and biochemical assays; Two human patients; fibroblast isotope tracing and genetic complementation limitations: DHTKD1 is the E1 component, not a stand-alone enzyme performing every complex reaction. [bezerra2020] Crystal structure and interaction studies of human DHTKD1 provide insight into a mitochondrial megacomplex in lysine catabolism (2020). https://pmc.ncbi.nlm.nih.gov/articles/PMC7340257/ DOI: 10.1107/S205225252000696X [danhauser2012] DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3516599/ DOI: 10.1016/j.ajhg.2012.10.006
    Complete structured claim and evidence

What acts on it

  1. Patient DHTKD1-deficient fibroblasts accumulated deuterium-labeled 2-oxoadipate from labeled lysine; wild-type DHTKD1 expression normalized the biochemical defect.

    DHTKD1 → 2-Oxoadipate source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    A B1-dependent enzyme connects lysine degradation to glutaryl-CoA metabolism.
    evidence
    [{"paper_key": "danhauser-2012-dhtkd1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
    experimental_model
    Patient fibroblasts, isotope tracing and lentiviral complementation.
    limitations
    Two individuals; neurological phenotypes vary and biochemical rescue does not prove a clinical treatment.
    nutrient
    Thiamine (vitamin B1) · Thiamine (vitamin B1)
    nutrient_topic
    Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
    organism
    Homo sapiens
    plain_language
    Replacing the faulty enzyme restored the tested metabolic step. The experiment identifies a machinery defect rather than a lack of dietary B1.
    primary_references
    [danhauser-2012-dhtkd1] DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria (2012). https://pubmed.ncbi.nlm.nih.gov/23141293/ DOI: 10.1016/j.ajhg.2012.10.006
    tissue_or_cell_type
    Cultured fibroblasts
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 909–921

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Patient fibroblasts, isotope tracing and lentiviral complementation. · source_derived_draft · unverified_draft

    ### b1-dhtkd1-patient-lysine-turnover Patient DHTKD1-deficient fibroblasts accumulated deuterium-labeled 2-oxoadipate from labeled lysine; wild-type DHTKD1 expression normalized the biochemical defect. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Replacing the faulty enzyme restored the tested metabolic step. The experiment identifies a machinery defect rather than a lack of dietary B1. organism: Homo sapiens tissue_or_cell_type: Cultured fibroblasts experimental_model: Patient fibroblasts, isotope tracing and lentiviral complementation. limitations: Two individuals; neurological phenotypes vary and biochemical rescue does not prove a clinical treatment. evidence: [{"paper_key": "danhauser-2012-dhtkd1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: A B1-dependent enzyme connects lysine degradation to glutaryl-CoA metabolism. nutrient: Thiamine (vitamin B1) [danhauser-2012-dhtkd1] DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria (2012). https://pubmed.ncbi.nlm.nih.gov/23141293/ DOI: 10.1016/j.ajhg.2012.10.006
    Complete structured claim and evidence

  2. Recombinant human DHTKD1 showed approximately 49-fold greater catalytic efficiency for 2-oxoadipate than 2-oxoglutarate in the reported assay.

    DHTKD1 → 2-Oxoadipate source_derived_draftungraded
    Experimental context and source evidence
    evidence
    [{"paper_key": "nemeria-2018-oadh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
    experimental_model
    Human enzyme substrate-kinetic comparison.
    limitations
    The approximately 49-fold value belongs to this preparation and assay; it is not universal tissue selectivity.
    nutrient
    Thiamine (vitamin B1) · Thiamine (vitamin B1)
    nutrient_topic
    Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
    organism
    Homo sapiens
    plain_language
    The two B1 enzymes overlap in possible substrates, but DHTKD1 is specialized for the longer amino-acid-derived ketoacid.
    primary_references
    [nemeria-2018-oadh] The mitochondrial 2-oxoadipate and 2-oxoglutarate dehydrogenase complexes share their E2 and E3 components for their function and both generate reactive oxygen species (2018). https://pubmed.ncbi.nlm.nih.gov/29191460/ DOI: 10.1016/j.freeradbiomed.2017.11.018
    tissue_or_cell_type
    Purified enzyme

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 883–894

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human enzyme substrate-kinetic comparison. · source_derived_draft · unverified_draft

    ### b1-dhtkd1-prefers-oxoadipate Recombinant human DHTKD1 showed approximately 49-fold greater catalytic efficiency for 2-oxoadipate than 2-oxoglutarate in the reported assay. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The two B1 enzymes overlap in possible substrates, but DHTKD1 is specialized for the longer amino-acid-derived ketoacid. organism: Homo sapiens tissue_or_cell_type: Purified enzyme experimental_model: Human enzyme substrate-kinetic comparison. limitations: The approximately 49-fold value belongs to this preparation and assay; it is not universal tissue selectivity. evidence: [{"paper_key": "nemeria-2018-oadh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] nutrient: Thiamine (vitamin B1) [nemeria-2018-oadh] The mitochondrial 2-oxoadipate and 2-oxoglutarate dehydrogenase complexes share their E2 and E3 components for their function and both generate reactive oxygen species (2018). https://pubmed.ncbi.nlm.nih.gov/29191460/ DOI: 10.1016/j.freeradbiomed.2017.11.018
    Complete structured claim and evidence

  3. PLP-dependent AADAT transfers the amino group from aminoadipate to 2-oxoglutarate, generating 2-oxoadipate and glutamate.

    L-alpha-Aminoadipate → 2-Oxoadipate source_derived_draftungraded
    Experimental context and source evidence
    experimental_model
    Human cDNA and recombinant bacterial expression; Purified recombinant human enzyme; kinetics and crystallography
    limitations
    AADAT also accepts other substrates; substrate breadth is not lysine-specific regulation.
    organism
    Homo sapiens
    plain_language
    AADAT removes the remaining amino group.
    primary_references
    [goh2002] Characterization of the human gene encoding alpha-aminoadipate aminotransferase (AADAT). (2002). https://pubmed.ncbi.nlm.nih.gov/12126930/ DOI: 10.1016/S1096-7192(02)00037-9 [han2008] Substrate specificity and structure of human aminoadipate aminotransferase/kynurenine aminotransferase II (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2559858/ DOI: 10.1042/BSR20080085
    tissue_or_cell_type
    Mitochondrial lysine catabolism; human expression highest in liver in cloning study

    L-Lysine: mechanism-first literature curation (2026-09-17) · lines 114–123

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cDNA and recombinant bacterial expression; Purified recombinant human enzyme; kinetics and crystallography · source_derived_draft · unverified_draft

    ### aadat-transamination PLP-dependent AADAT transfers the amino group from aminoadipate to 2-oxoglutarate, generating 2-oxoadipate and glutamate. Plain language: AADAT removes the remaining amino group. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial lysine catabolism; human expression highest in liver in cloning study experimental_model: Human cDNA and recombinant bacterial expression; Purified recombinant human enzyme; kinetics and crystallography limitations: AADAT also accepts other substrates; substrate breadth is not lysine-specific regulation. [goh2002] Characterization of the human gene encoding alpha-aminoadipate aminotransferase (AADAT). (2002). https://pubmed.ncbi.nlm.nih.gov/12126930/ DOI: 10.1016/S1096-7192(02)00037-9 [han2008] Substrate specificity and structure of human aminoadipate aminotransferase/kynurenine aminotransferase II (2008). https://pmc.ncbi.nlm.nih.gov/articles/PMC2559858/ DOI: 10.1042/BSR20080085
    Complete structured claim and evidence

  4. DHTKD1-deficient patient fibroblasts accumulate lysine-derived 2-oxoadipate; wild-type complementation restores its disposal.

    DHTKD1 → 2-Oxoadipate source_derived_draftungraded
    Experimental context and source evidence
    affected_machinery
    Oxoadipate-dehydrogenase E1
    availability_state
    machinery_impairment Imported condition classification; unverified.
    deficiency_not_equivalent
    Dietary lysine deficiency
    experimental_model
    Two human patients and isotope-traced fibroblasts
    limitations
    Biochemical causation is stronger than attribution of every neurological finding.
    organism
    Homo sapiens
    plain_language
    A downstream enzyme defect leaves oxoadipate uncleared.
    primary_references
    [danhauser2012] DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3516599/ DOI: 10.1016/j.ajhg.2012.10.006
    tissue_or_cell_type
    Fibroblasts; clinical aciduria
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Lysine: mechanism-first literature curation (2026-09-17) · lines 278–288

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two human patients and isotope-traced fibroblasts · source_derived_draft · unverified_draft

    ### dhtkd1-oxoadipate-accumulation DHTKD1-deficient patient fibroblasts accumulate lysine-derived 2-oxoadipate; wild-type complementation restores its disposal. Plain language: A downstream enzyme defect leaves oxoadipate uncleared. Condition category: machinery_impairment organism: Homo sapiens tissue_or_cell_type: Fibroblasts; clinical aciduria experimental_model: Two human patients and isotope-traced fibroblasts limitations: Biochemical causation is stronger than attribution of every neurological finding. affected_machinery: Oxoadipate-dehydrogenase E1 deficiency_not_equivalent: Dietary lysine deficiency [danhauser2012] DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3516599/ DOI: 10.1016/j.ajhg.2012.10.006
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Human DHTKD1 supported 2-oxoadipate dehydrogenase activity when combined with the DLST and DLD components also used by OGDH.

    DHTKD1 → 2-Oxoadipate dehydrogenase complex source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    B1-dependent lysine catabolism converges on the same lipoyl, CoA and NAD/FAD machinery used in OGDH.
    evidence
    [{"paper_key": "nemeria-2018-oadh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
    experimental_model
    Human recombinant component reconstitution.
    limitations
    Reconstituted proteins; sharing does not establish competition for limiting subunits in vivo.
    nutrient
    Thiamine (vitamin B1) · Thiamine (vitamin B1)
    nutrient_topic
    Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
    organism
    Homo sapiens
    plain_language
    Lysine-related carbon disposal uses a different B1-dependent E1, while sharing the downstream E2 and E3 proteins with a TCA-cycle enzyme.
    primary_references
    [nemeria-2018-oadh] The mitochondrial 2-oxoadipate and 2-oxoglutarate dehydrogenase complexes share their E2 and E3 components for their function and both generate reactive oxygen species (2018). https://pubmed.ncbi.nlm.nih.gov/29191460/ DOI: 10.1016/j.freeradbiomed.2017.11.018
    tissue_or_cell_type
    Purified complex

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 869–881

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human recombinant component reconstitution. · source_derived_draft · unverified_draft

    ### b1-dhtkd1-recruits-shared-dlst-dld Human DHTKD1 supported 2-oxoadipate dehydrogenase activity when combined with the DLST and DLD components also used by OGDH. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Lysine-related carbon disposal uses a different B1-dependent E1, while sharing the downstream E2 and E3 proteins with a TCA-cycle enzyme. organism: Homo sapiens tissue_or_cell_type: Purified complex experimental_model: Human recombinant component reconstitution. limitations: Reconstituted proteins; sharing does not establish competition for limiting subunits in vivo. evidence: [{"paper_key": "nemeria-2018-oadh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1-dependent lysine catabolism converges on the same lipoyl, CoA and NAD/FAD machinery used in OGDH. nutrient: Thiamine (vitamin B1) [nemeria-2018-oadh] The mitochondrial 2-oxoadipate and 2-oxoglutarate dehydrogenase complexes share their E2 and E3 components for their function and both generate reactive oxygen species (2018). https://pubmed.ncbi.nlm.nih.gov/29191460/ DOI: 10.1016/j.freeradbiomed.2017.11.018
    Complete structured claim and evidence

  2. The human DHTKD1 dimer structure places ThDP-containing active sites at the subunit interface and reveals a pocket compatible with the longer 2-oxoadipate substrate.

    DHTKD1 → Thiamine diphosphate source_derived_draftungraded
    Experimental context and source evidence
    evidence
    [{"paper_key": "bezerra-2020-dhtkd1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-44"], "locator": "not included in the deposited", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
    experimental_model
    1.9-A human DHTKD1 crystal structure.
    limitations
    Substrate-pocket interpretation is structural; an uncertain putative 2-oxoadipate density was not deposited as ligand.
    nutrient
    Thiamine (vitamin B1) · Thiamine (vitamin B1)
    nutrient_topic
    Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
    organism
    Homo sapiens
    plain_language
    DHTKD1 is its own B1 enzyme. Similarity to OGDH does not make the proteins interchangeable.
    primary_references
    [bezerra-2020-dhtkd1] Crystal structure and interaction studies of human DHTKD1 provide insight into a mitochondrial megacomplex in lysine catabolism (2020). https://pubmed.ncbi.nlm.nih.gov/32695416/ DOI: 10.1107/s205225252000696x
    tissue_or_cell_type
    Recombinant protein crystal

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 896–907

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 1.9-A human DHTKD1 crystal structure. · source_derived_draft · unverified_draft

    ### b1-dhtkd1-thdp-dimer-sites The human DHTKD1 dimer structure places ThDP-containing active sites at the subunit interface and reveals a pocket compatible with the longer 2-oxoadipate substrate. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: DHTKD1 is its own B1 enzyme. Similarity to OGDH does not make the proteins interchangeable. organism: Homo sapiens tissue_or_cell_type: Recombinant protein crystal experimental_model: 1.9-A human DHTKD1 crystal structure. limitations: Substrate-pocket interpretation is structural; an uncertain putative 2-oxoadipate density was not deposited as ligand. evidence: [{"paper_key": "bezerra-2020-dhtkd1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-44"], "locator": "not included in the deposited", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] nutrient: Thiamine (vitamin B1) [bezerra-2020-dhtkd1] Crystal structure and interaction studies of human DHTKD1 provide insight into a mitochondrial megacomplex in lysine catabolism (2020). https://pubmed.ncbi.nlm.nih.gov/32695416/ DOI: 10.1107/s205225252000696x
    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