Component

4-Methyl-2-oxopentanoate / alpha-ketoisocaproate

Leucine-derived branched-chain alpha-ketoacid.

5 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. Prolonged alanine culture reduced subsequent acute alanine-stimulated insulin secretion by 74%, without reducing responses to glucose, KCl or ketoisocaproate; 18 hours without alanine partly restored responsiveness.

    L-Alanine → Alanine-stimulated insulin secretion in BRIN-BD11 cells source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Rat BRIN-BD11 culture, washout and rechallenge experiments.
    limitations
    Exposure concentration/duration before washout are not resolved in the accessed abstract; no human chronic-use threshold is inferred.
    nutrient_topic
    L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
    plain_language
    A strong acute response need not persist after prolonged exposure.
    primary_references
    Prolonged L-alanine exposure induces changes in metabolism, Ca(2+) handling and desensitization of insulin secretion in clonal pancreatic beta-cells. · 2009 · https://pubmed.ncbi.nlm.nih.gov/18702613/ · DOI 10.1042/CS20080138

    L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 400–406

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Rat BRIN-BD11 culture, washout and rechallenge experiments. · source_derived_draft · unverified_draft

    ## alanine-beta-chronic-desensitization A strong acute response need not persist after prolonged exposure. Prolonged alanine culture reduced subsequent acute alanine-stimulated insulin secretion by 74%, without reducing responses to glucose, KCl or ketoisocaproate; 18 hours without alanine partly restored responsiveness. Model: Rat BRIN-BD11 culture, washout and rechallenge experiments. Limitations: Exposure concentration/duration before washout are not resolved in the accessed abstract; no human chronic-use threshold is inferred. Evidence access: Primary abstract Prolonged L-alanine exposure induces changes in metabolism, Ca(2+) handling and desensitization of insulin secretion in clonal pancreatic beta-cells. · 2009 · https://pubmed.ncbi.nlm.nih.gov/18702613/ · DOI 10.1042/CS20080138
    Complete structured claim and evidence

  2. Alanine augmented insulin release evoked by leucine or 2-ketoisocaproate in normal adult rat islets, while not significantly changing glucose-induced secretion.

    L-Alanine → Insulin secretion from normal adult rat islets source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Isolated normal adult rat islets.
    limitations
    This setting differs from clonal cells; model and substrate conditions are retained rather than treated as an unexplained contradiction.
    nutrient_topic
    L-Alanine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Alanine
    plain_language
    The accompanying nutrient changed whether alanine increased insulin.
    primary_references
    The stimulus-secretion coupling of amino acid-induced insulin release. Insulinotropic action of L-alanine. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12383948/ · DOI 10.1016/s0304-4165(02)00337-9

    L-Alanine: carbon, nitrogen, protein synthesis and cross-nutrient mechanisms (2026-09-19) · lines 376–382

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Isolated normal adult rat islets. · source_derived_draft · unverified_draft

    ## alanine-islet-leucine-combination The accompanying nutrient changed whether alanine increased insulin. Alanine augmented insulin release evoked by leucine or 2-ketoisocaproate in normal adult rat islets, while not significantly changing glucose-induced secretion. Model: Isolated normal adult rat islets. Limitations: This setting differs from clonal cells; model and substrate conditions are retained rather than treated as an unexplained contradiction. Evidence access: Primary abstract The stimulus-secretion coupling of amino acid-induced insulin release. Insulinotropic action of L-alanine. · 2002 · https://pubmed.ncbi.nlm.nih.gov/12383948/ · DOI 10.1016/s0304-4165(02)00337-9
    Complete structured claim and evidence

  3. Human BCAT1 transfers the leucine amino group to 2-oxoglutarate, producing alpha-ketoisocaproate and glutamate.

    Human cytosolic branched-chain aminotransferase / BCAT1 → L-Leucine source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Essential amino-acid nitrogen transfer; net direction depends on substrate/product conditions.
    experimental_model
    Recombinant human BCAT1 and BCAT2; pre-steady-state kinetics and structures
    limitations
    Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds.
    nutrient_topic
    Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
    organism
    Homo sapiens
    plain_language
    B6-dependent transamination starts leucine processing and transfers nitrogen to glutamate.
    primary_references
    [b6-bcat1-2005] Structural determinants for branched-chain aminotransferase isozyme-specific inhibition by the anticonvulsant drug gabapentin (2005). https://pubmed.ncbi.nlm.nih.gov/16141215/ DOI: 10.1074/jbc.M506486200
    tissue_or_cell_type
    Purified recombinant protein; no intact tissue

    Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 717–727

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human BCAT1 and BCAT2; pre-steady-state kinetics and structures · source_derived_draft · unverified_draft

    ### b6-met-bcat1-leucine Human BCAT1 transfers the leucine amino group to 2-oxoglutarate, producing alpha-ketoisocaproate and glutamate. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6-dependent transamination starts leucine processing and transfers nitrogen to glutamate. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human BCAT1 and BCAT2; pre-steady-state kinetics and structures limitations: Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds. cross_nutrient: Essential amino-acid nitrogen transfer; net direction depends on substrate/product conditions. [b6-bcat1-2005] Structural determinants for branched-chain aminotransferase isozyme-specific inhibition by the anticonvulsant drug gabapentin (2005). https://pubmed.ncbi.nlm.nih.gov/16141215/ DOI: 10.1074/jbc.M506486200
    Complete structured claim and evidence

  4. Human BCAT2 transfers the leucine amino group to 2-oxoglutarate, producing alpha-ketoisocaproate and glutamate.

    Human mitochondrial branched-chain aminotransferase / BCAT2 → L-Leucine source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Essential amino-acid nitrogen transfer; net direction depends on substrate/product conditions.
    experimental_model
    Recombinant human BCAT1 and BCAT2; pre-steady-state kinetics and structures
    limitations
    Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds.
    nutrient_topic
    Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B6
    organism
    Homo sapiens
    plain_language
    B6-dependent transamination starts leucine processing and transfers nitrogen to glutamate.
    primary_references
    [b6-bcat1-2005] Structural determinants for branched-chain aminotransferase isozyme-specific inhibition by the anticonvulsant drug gabapentin (2005). https://pubmed.ncbi.nlm.nih.gov/16141215/ DOI: 10.1074/jbc.M506486200
    tissue_or_cell_type
    Purified recombinant protein; no intact tissue

    Vitamin B6: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 729–739

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human BCAT1 and BCAT2; pre-steady-state kinetics and structures · source_derived_draft · unverified_draft

    ### b6-met-bcat2-leucine Human BCAT2 transfers the leucine amino group to 2-oxoglutarate, producing alpha-ketoisocaproate and glutamate. Condition category: normal nutrient_topic: Vitamin B6 research collection; topical membership is not evidence of a direct dietary effect. plain_language: B6-dependent transamination starts leucine processing and transfers nitrogen to glutamate. organism: Homo sapiens tissue_or_cell_type: Purified recombinant protein; no intact tissue experimental_model: Recombinant human BCAT1 and BCAT2; pre-steady-state kinetics and structures limitations: Purified-enzyme evidence does not define dietary requirements or cellular PLP thresholds. cross_nutrient: Essential amino-acid nitrogen transfer; net direction depends on substrate/product conditions. [b6-bcat1-2005] Structural determinants for branched-chain aminotransferase isozyme-specific inhibition by the anticonvulsant drug gabapentin (2005). https://pubmed.ncbi.nlm.nih.gov/16141215/ DOI: 10.1074/jbc.M506486200
    Complete structured claim and evidence

  5. Total plasma branched-chain alpha-ketoacids were 2.7 times control after thiamine deprivation, without a significant reported correlation to liver thiamine.

    Thiamine (vitamin B1) → Plasma total branched-chain alpha-ketoacid concentration source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    cross_nutrient
    B1 deprivation changes metabolites of three essential amino acids.
    evidence
    [{"paper_key": "shigematsu-1989-bcaa", "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
    Four-week dietary depletion.
    limitations
    Do not infer a linear liver-thiamine/ketoacid relationship or human MSUD equivalence.
    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
    Rattus norvegicus
    plain_language
    Ketoacid accumulation is compatible with impaired disposal, but this pool measurement is not a direct flux assay.
    primary_references
    [shigematsu-1989-bcaa] Branched-chain alpha-ketoacids and related acids in thiamin-deprived rats (1989). https://pubmed.ncbi.nlm.nih.gov/2760689/ DOI: 10.3177/jnsv.35.163
    tissue_or_cell_type
    Plasma; liver thiamine measured
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 828–840

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four-week dietary depletion. · source_derived_draft · unverified_draft

    ### b1-deficiency-plasma-bcka-rise Total plasma branched-chain alpha-ketoacids were 2.7 times control after thiamine deprivation, without a significant reported correlation to liver thiamine. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Ketoacid accumulation is compatible with impaired disposal, but this pool measurement is not a direct flux assay. organism: Rattus norvegicus tissue_or_cell_type: Plasma; liver thiamine measured experimental_model: Four-week dietary depletion. limitations: Do not infer a linear liver-thiamine/ketoacid relationship or human MSUD equivalence. evidence: [{"paper_key": "shigematsu-1989-bcaa", "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 deprivation changes metabolites of three essential amino acids. nutrient: Thiamine (vitamin B1) [shigematsu-1989-bcaa] Branched-chain alpha-ketoacids and related acids in thiamin-deprived rats (1989). https://pubmed.ncbi.nlm.nih.gov/2760689/ DOI: 10.3177/jnsv.35.163
    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.

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