Component

Branched-chain ketoacid dehydrogenase E1 alpha / BCKDHA

Human alpha subunit of BCKDH E1.

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

Where it participates (unsigned role)

  1. The isoleucine pathway in the primary biochemical study places BCKDH-mediated oxidative decarboxylation of the branched ketoacid upstream of 2-methylbutyryl-CoA.

    Human branched-chain alpha-ketoacid dehydrogenase complex → 2-Methylbutyryl-CoA source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text, pathway background
    experimental_model
    Established pathway shown in a human ECHS1 disease/biochemistry study; not a new BCKDH assay in that paper.
    limitations
    Cofactor and catalytic evidence is separately linked from existing ThDP/DLD records.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    A shared BCAA enzyme commits the carbon skeleton to further breakdown.
    primary_references
    Clinical and biochemical characterization of four patients with mutations in ECHS1. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26081110/ · DOI 10.1186/s13023-015-0290-1

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 170–176

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Established pathway shown in a human ECHS1 disease/biochemistry study; not a new BCKDH assay in that paper. · source_derived_draft · unverified_draft

    ## isoleucine-bckdh-carbon-step A shared BCAA enzyme commits the carbon skeleton to further breakdown. The isoleucine pathway in the primary biochemical study places BCKDH-mediated oxidative decarboxylation of the branched ketoacid upstream of 2-methylbutyryl-CoA. Model: Established pathway shown in a human ECHS1 disease/biochemistry study; not a new BCKDH assay in that paper. Limitations: Cofactor and catalytic evidence is separately linked from existing ThDP/DLD records. Evidence access: Primary full text, pathway background Clinical and biochemical characterization of four patients with mutations in ECHS1. · 2015 · https://pubmed.ncbi.nlm.nih.gov/26081110/ · DOI 10.1186/s13023-015-0290-1
    Complete structured claim and evidence

  2. BCKDK phosphorylates BCKDH E1-alpha; inactivating human BCKDK variants reduced E1-alpha phosphorylation and circulating BCAAs.

    Human branched-chain ketoacid dehydrogenase kinase / BCKDK → Human branched-chain alpha-ketoacid dehydrogenase complex source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Human families with biallelic BCKDK variants and supporting mouse experiments.
    limitations
    This is a rare genetic syndrome, not a general explanation for autism.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    A kinase normally slows amino-acid breakdown.
    primary_references
    Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22956686/ · DOI 10.1126/science.1224631
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 258–264

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human families with biallelic BCKDK variants and supporting mouse experiments. · source_derived_draft · unverified_draft

    ## isoleucine-bckdk-brake A kinase normally slows amino-acid breakdown. BCKDK phosphorylates BCKDH E1-alpha; inactivating human BCKDK variants reduced E1-alpha phosphorylation and circulating BCAAs. Model: Human families with biallelic BCKDK variants and supporting mouse experiments. Limitations: This is a rare genetic syndrome, not a general explanation for autism. Evidence access: Primary abstract Mutations in BCKD-kinase lead to a potentially treatable form of autism with epilepsy. · 2012 · https://pubmed.ncbi.nlm.nih.gov/22956686/ · DOI 10.1126/science.1224631
    Complete structured claim and evidence

  3. Human supraclavicular BAT SLC25A44 mRNA increased after cold exposure and correlated with UCP1 and BCKDHA expression.

    Controlled cold exposure in the human BAT study → Human mitochondrial BCAA carrier / SLC25A44 source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Human cold-exposure BAT samples; expression correlations.
    limitations
    Observational expression evidence, not transporter gene manipulation or proof of isoleucine-specific clearance in humans.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    Human tissue showed a coordinated change in the shared catabolic system.
    primary_references
    BCAA catabolism in brown fat controls energy homeostasis through SLC25A44. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31435015/ · DOI 10.1038/s41586-019-1503-x

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 58–64

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human cold-exposure BAT samples; expression correlations. · source_derived_draft · unverified_draft

    ## isoleucine-human-bat-carrier Human tissue showed a coordinated change in the shared catabolic system. Human supraclavicular BAT SLC25A44 mRNA increased after cold exposure and correlated with UCP1 and BCKDHA expression. Model: Human cold-exposure BAT samples; expression correlations. Limitations: Observational expression evidence, not transporter gene manipulation or proof of isoleucine-specific clearance in humans. Evidence access: Primary full text BCAA catabolism in brown fat controls energy homeostasis through SLC25A44. · 2019 · https://pubmed.ncbi.nlm.nih.gov/31435015/ · DOI 10.1038/s41586-019-1503-x
    Complete structured claim and evidence

  4. Human BCKDH E1 decarboxylates a branched-chain alpha-ketoacid using ThDP and reductively acylates the lipoylated DBT domain.

    Human branched-chain ketoacid dehydrogenase E1 → Dihydrolipoyl branched-chain transacylase / DBT source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Thiamine and protein-bound lipoate connect branched-chain amino-acid catabolism; CoA and DLD act later.
    evidence
    [{"paper_key": "li-2004-bckdh", "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
    Recombinant human E1b and E2b lipoyl domain assays.
    limitations
    Purified-system evidence; nutritional response was not tested.
    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
    B1 helps process ketoacids formed from branched-chain amino acids; the acyl fragment then moves to a lipoyl carrier on E2.
    primary_references
    [li-2004-bckdh] Cross-talk between thiamin diphosphate binding and phosphorylation loop conformation in human branched-chain alpha-keto acid decarboxylase/dehydrogenase (2004). https://pubmed.ncbi.nlm.nih.gov/15166214/ DOI: 10.1074/jbc.m403611200
    tissue_or_cell_type
    Purified proteins

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 773–785

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human E1b and E2b lipoyl domain assays. · source_derived_draft · unverified_draft

    ### b1-bckdh-ketoacid-acylation Human BCKDH E1 decarboxylates a branched-chain alpha-ketoacid using ThDP and reductively acylates the lipoylated DBT domain. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 helps process ketoacids formed from branched-chain amino acids; the acyl fragment then moves to a lipoyl carrier on E2. organism: Homo sapiens tissue_or_cell_type: Purified proteins experimental_model: Recombinant human E1b and E2b lipoyl domain assays. limitations: Purified-system evidence; nutritional response was not tested. evidence: [{"paper_key": "li-2004-bckdh", "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: Thiamine and protein-bound lipoate connect branched-chain amino-acid catabolism; CoA and DLD act later. nutrient: Thiamine (vitamin B1) [li-2004-bckdh] Cross-talk between thiamin diphosphate binding and phosphorylation loop conformation in human branched-chain alpha-keto acid decarboxylase/dehydrogenase (2004). https://pubmed.ncbi.nlm.nih.gov/15166214/ DOI: 10.1074/jbc.m403611200
    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