Component

L-Valine

Branched-chain essential amino acid.

26 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. Valine supplementation restored translation and proliferation during severe isoleucine deprivation in healthy fibroblasts but not in the tested IARS1-deficient fibroblasts.

    L-Valine → Protein translation in human fibroblasts source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Human fibroblast experiments; representative low isoleucine 1.02 micromolar and high valine 2330 micromolar conditions.
    limitations
    Culture conditions are not a recommended dietary ratio; two patient lines shared the investigated variants.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    The rescue required functioning charging machinery.
    primary_references
    Isoleucine-to-valine substitutions support cellular physiology during isoleucine deprivation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39657787/ · DOI 10.1093/nar/gkae1184
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 122–128

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human fibroblast experiments; representative low isoleucine 1.02 micromolar and high valine 2330 micromolar conditions. · source_derived_draft · unverified_draft

    ## isoleucine-valine-translation-rescue The rescue required functioning charging machinery. Valine supplementation restored translation and proliferation during severe isoleucine deprivation in healthy fibroblasts but not in the tested IARS1-deficient fibroblasts. Model: Human fibroblast experiments; representative low isoleucine 1.02 micromolar and high valine 2330 micromolar conditions. Limitations: Culture conditions are not a recommended dietary ratio; two patient lines shared the investigated variants. Evidence access: Primary full text Isoleucine-to-valine substitutions support cellular physiology during isoleucine deprivation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39657787/ · DOI 10.1093/nar/gkae1184
    Complete structured claim and evidence

  2. Carbon-13 valine supplied the lipogenic propionyl-CoA precursor in cultured 3T3-L1 adipocytes.

    L-Valine → Propionyl-CoA source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    true
    evidence_location
    Full text Results; Figures 6-8 and isotope model
    experimental_model
    Differentiated mouse 3T3-L1 adipocytes
    exposure
    24-hour [U-13C]valine tracing
    limitations
    Mouse cell culture; isotope labeling and model assumptions do not establish human dietary carbon fractions.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Mus musculus
    plain_language
    Mouse fat-cell tracing placed valine carbon into the precursor that can enter B12-dependent metabolism or odd-chain fat synthesis.
    primary_references
    [crown-2015-bcaa-fatty-acids] Catabolism of Branched Chain Amino Acids Contributes Significantly to Synthesis of Odd-Chain and Even-Chain Fatty Acids in 3T3-L1 Adipocytes. (2015). https://pubmed.ncbi.nlm.nih.gov/26710334/ DOI: 10.1371/journal.pone.0145850
    tissue_or_cell_type
    Adipocytes

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1216–1228

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Differentiated mouse 3T3-L1 adipocytes · source_derived_draft · unverified_draft

    ### valine-propionyl-coa-lipogenesis Carbon-13 valine supplied the lipogenic propionyl-CoA precursor in cultured 3T3-L1 adipocytes. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mouse fat-cell tracing placed valine carbon into the precursor that can enter B12-dependent metabolism or odd-chain fat synthesis. organism: Mus musculus tissue_or_cell_type: Adipocytes experimental_model: Differentiated mouse 3T3-L1 adipocytes limitations: Mouse cell culture; isotope labeling and model assumptions do not establish human dietary carbon fractions. exposure: 24-hour [U-13C]valine tracing cross_nutrient: true evidence_location: Full text Results; Figures 6-8 and isotope model [crown-2015-bcaa-fatty-acids] Catabolism of Branched Chain Amino Acids Contributes Significantly to Synthesis of Odd-Chain and Even-Chain Fatty Acids in 3T3-L1 Adipocytes. (2015). https://pubmed.ncbi.nlm.nih.gov/26710334/ DOI: 10.1371/journal.pone.0145850
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Human ACADSB supported oxidation of 2-methylbutyryl-CoA; patient fibroblast assays and expression studies distinguished this isoleucine enzyme from valine-related ACAD8.

    Human short/branched-chain acyl-CoA dehydrogenase / ACADSB → 2-Methylbutyryl-CoA source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Human fibroblasts, sequence analysis and recombinant expression.
    limitations
    Does not make ACADSB and ACAD8 interchangeable.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    Isoleucine and valine split into different enzyme routes after their shared early steps.
    primary_references
    Isolated 2-methylbutyrylglycinuria caused by short/branched-chain acyl-CoA dehydrogenase deficiency: identification of a new enzyme defect, resolution of its molecular basis, and evidence for distinct acyl-CoA dehydrogenases in isoleucine and valine metabolism. · 2000 · https://pubmed.ncbi.nlm.nih.gov/11013134/ · DOI 10.1086/303105

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 178–184

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human fibroblasts, sequence analysis and recombinant expression. · source_derived_draft · unverified_draft

    ## isoleucine-acadsb-reaction Isoleucine and valine split into different enzyme routes after their shared early steps. Human ACADSB supported oxidation of 2-methylbutyryl-CoA; patient fibroblast assays and expression studies distinguished this isoleucine enzyme from valine-related ACAD8. Model: Human fibroblasts, sequence analysis and recombinant expression. Limitations: Does not make ACADSB and ACAD8 interchangeable. Evidence access: Primary abstract Isolated 2-methylbutyrylglycinuria caused by short/branched-chain acyl-CoA dehydrogenase deficiency: identification of a new enzyme defect, resolution of its molecular basis, and evidence for distinct acyl-CoA dehydrogenases in isoleucine and valine metabolism. · 2000 · https://pubmed.ncbi.nlm.nih.gov/11013134/ · DOI 10.1086/303105
    Complete structured claim and evidence

  2. A single 0.3 g/kg oral isoleucine dose reduced glucose at 30 and 60 minutes after a 2 g/kg glucose bolus in rats.

    L-Isoleucine → Rat plasma glucose after oral glucose challenge source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Normal rats; BCAAs compared at matched doses.
    limitations
    Not a human diabetes intervention or equivalent to prolonged high-isoleucine feeding.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    An acute dose changed the handling of a glucose challenge.
    primary_references
    Isoleucine, a potent plasma glucose-lowering amino acid, stimulates glucose uptake in C2C12 myotubes. · 2003 · https://pubmed.ncbi.nlm.nih.gov/14651987/ · DOI 10.1016/j.bbrc.2003.11.039

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 338–344

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Normal rats; BCAAs compared at matched doses. · source_derived_draft · unverified_draft

    ## isoleucine-acute-rat-glucose An acute dose changed the handling of a glucose challenge. A single 0.3 g/kg oral isoleucine dose reduced glucose at 30 and 60 minutes after a 2 g/kg glucose bolus in rats. Model: Normal rats; BCAAs compared at matched doses. Limitations: Not a human diabetes intervention or equivalent to prolonged high-isoleucine feeding. Evidence access: Primary abstract Isoleucine, a potent plasma glucose-lowering amino acid, stimulates glucose uptake in C2C12 myotubes. · 2003 · https://pubmed.ncbi.nlm.nih.gov/14651987/ · DOI 10.1016/j.bbrc.2003.11.039
    Complete structured claim and evidence

  3. BAT-specific Slc25a44 knockout impaired BCAA clearance and insulin tolerance without a significant difference in energy expenditure or body weight in this study.

    Mouse mitochondrial BCAA carrier / Slc25a44 → Systemic insulin tolerance supported by mouse BAT source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Conditional mouse knockout under defined temperature and diet conditions.
    limitations
    Different perturbations and conditions from prior Bckdha-loss thermogenesis work; no universal requirement for a weight change.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    The metabolic effect was separable from measured heat production and weight.
    primary_references
    BCAA-nitrogen flux in brown fat controls metabolic health independent of thermogenesis. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38653240/ · DOI 10.1016/j.cell.2024.03.030
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 98–104

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Conditional mouse knockout under defined temperature and diet conditions. · source_derived_draft · unverified_draft

    ## isoleucine-bat-insulin-beyond-heat The metabolic effect was separable from measured heat production and weight. BAT-specific Slc25a44 knockout impaired BCAA clearance and insulin tolerance without a significant difference in energy expenditure or body weight in this study. Model: Conditional mouse knockout under defined temperature and diet conditions. Limitations: Different perturbations and conditions from prior Bckdha-loss thermogenesis work; no universal requirement for a weight change. Evidence access: Primary full text BCAA-nitrogen flux in brown fat controls metabolic health independent of thermogenesis. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38653240/ · DOI 10.1016/j.cell.2024.03.030
    Complete structured claim and evidence

  4. Isoleucine at 80-200 micromolar and valine at 250-500 micromolar reduced leucine transamination/oxidation by up to 25% in human peripheral lymphocytes.

    L-Isoleucine → Leucine transamination and oxidation in human lymphocytes source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Isolated human lymphocyte concentration-response assays.
    limitations
    Does not quantify whole-body competition after a meal or prove a nutritional deficiency.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    Shared breakdown machinery can create substrate interactions.
    primary_references
    Assessment of effects of amino acids and branched chain keto acids on leucine oxidation in human lymphocytes. · 1988 · https://pubmed.ncbi.nlm.nih.gov/2905828/ · DOI 10.3109/00365518809085769

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 290–296

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Isolated human lymphocyte concentration-response assays. · source_derived_draft · unverified_draft

    ## isoleucine-bcaa-competition Shared breakdown machinery can create substrate interactions. Isoleucine at 80-200 micromolar and valine at 250-500 micromolar reduced leucine transamination/oxidation by up to 25% in human peripheral lymphocytes. Model: Isolated human lymphocyte concentration-response assays. Limitations: Does not quantify whole-body competition after a meal or prove a nutritional deficiency. Evidence access: Primary abstract Assessment of effects of amino acids and branched chain keto acids on leucine oxidation in human lymphocytes. · 1988 · https://pubmed.ncbi.nlm.nih.gov/2905828/ · DOI 10.3109/00365518809085769
    Complete structured claim and evidence

  5. Impaired mitochondrial BCAA nitrogen flux reduced synthesis of downstream metabolites including glutathione and increased oxidative stress in the tested BAT system.

    Mouse mitochondrial BCAA carrier / Slc25a44 → Glutathione synthesis in mouse brown adipocytes source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Mouse BAT carrier-loss and isotope/metabolite experiments.
    limitations
    Does not establish isoleucine supplementation as a glutathione intervention; the traced amino acids and cell context remain explicit.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    Transport and nitrogen handling can affect antioxidant production.
    primary_references
    BCAA-nitrogen flux in brown fat controls metabolic health independent of thermogenesis. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38653240/ · DOI 10.1016/j.cell.2024.03.030
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 90–96

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse BAT carrier-loss and isotope/metabolite experiments. · source_derived_draft · unverified_draft

    ## isoleucine-bcaa-glutathione Transport and nitrogen handling can affect antioxidant production. Impaired mitochondrial BCAA nitrogen flux reduced synthesis of downstream metabolites including glutathione and increased oxidative stress in the tested BAT system. Model: Mouse BAT carrier-loss and isotope/metabolite experiments. Limitations: Does not establish isoleucine supplementation as a glutathione intervention; the traced amino acids and cell context remain explicit. Evidence access: Primary full text BCAA-nitrogen flux in brown fat controls metabolic health independent of thermogenesis. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38653240/ · DOI 10.1016/j.cell.2024.03.030
    Complete structured claim and evidence

  6. Nitrogen-labeled valine and leucine supplied glutamate and alanine rapidly in brown-adipocyte tracing experiments.

    BCAA nitrogen flux in mouse brown adipocytes → L-Glutamate source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Mouse brown adipocytes with 15N-valine/leucine; cellular tracing.
    limitations
    Isoleucine is a connected BCAA substrate, but was not the tracer in these experiments.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    Shared BCAA chemistry carries nitrogen as well as carbon.
    primary_references
    BCAA-nitrogen flux in brown fat controls metabolic health independent of thermogenesis. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38653240/ · DOI 10.1016/j.cell.2024.03.030

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 82–88

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse brown adipocytes with 15N-valine/leucine; cellular tracing. · source_derived_draft · unverified_draft

    ## isoleucine-bcaa-nitrogen Shared BCAA chemistry carries nitrogen as well as carbon. Nitrogen-labeled valine and leucine supplied glutamate and alanine rapidly in brown-adipocyte tracing experiments. Model: Mouse brown adipocytes with 15N-valine/leucine; cellular tracing. Limitations: Isoleucine is a connected BCAA substrate, but was not the tracer in these experiments. Evidence access: Primary full text BCAA-nitrogen flux in brown fat controls metabolic health independent of thermogenesis. · 2024 · https://pubmed.ncbi.nlm.nih.gov/38653240/ · DOI 10.1016/j.cell.2024.03.030
    Complete structured claim and evidence

  7. 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

  8. Dietary BCAA supplementation improved neurobehavioral abnormalities in Bckdk-knockout mice.

    Dietary BCAA supplementation in Bckdk-deficient mice → Neurobehavioral phenotype in Bckdk-deficient mice source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Bckdk-knockout mouse dietary rescue.
    limitations
    Mixture intervention; cannot assign rescue uniquely to isoleucine or infer benefit in unrelated disorders.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    Replacing the shared substrates helped in the excessive-breakdown model.
    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 266–272

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Bckdk-knockout mouse dietary rescue. · source_derived_draft · unverified_draft

    ## isoleucine-bckdk-mouse-rescue Replacing the shared substrates helped in the excessive-breakdown model. Dietary BCAA supplementation improved neurobehavioral abnormalities in Bckdk-knockout mice. Model: Bckdk-knockout mouse dietary rescue. Limitations: Mixture intervention; cannot assign rescue uniquely to isoleucine or infer benefit in unrelated disorders. 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

  9. BAT-specific BCAA catabolic impairment reduced BCAA clearance and thermogenic fuel oxidation and promoted glucose intolerance in the tested mice.

    Mouse branched-chain alpha-ketoacid dehydrogenase complex → Systemic BCAA clearance supported by mouse BAT source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Mouse BAT-targeted Bckdha manipulation and metabolic assays.
    limitations
    Mixed BCAA pathway; not a claim that isolated isoleucine intake causes obesity.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    Loss of a tissue processing route changed whole-body amino-acid handling.
    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
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 66–72

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse BAT-targeted Bckdha manipulation and metabolic assays. · source_derived_draft · unverified_draft

    ## isoleucine-brown-fat-catabolic-loss Loss of a tissue processing route changed whole-body amino-acid handling. BAT-specific BCAA catabolic impairment reduced BCAA clearance and thermogenic fuel oxidation and promoted glucose intolerance in the tested mice. Model: Mouse BAT-targeted Bckdha manipulation and metabolic assays. Limitations: Mixed BCAA pathway; not a claim that isolated isoleucine intake causes obesity. 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

  10. ECHS1-deficient patients showed a dominant valine-metabolism defect rather than the expected isolated isoleucine block; liver retained tiglyl-CoA hydration capacity.

    Short-chain enoyl-CoA hydratase / ECHS1 → Tiglyl-CoA processing capacity in human tissues source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Four-patient biochemical study with tissue enzyme comparisons.
    limitations
    Does not establish the same backup capacity in every cell type.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    A pathway diagram alone can overstate an enzyme as an unavoidable gate.
    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
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 202–208

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Four-patient biochemical study with tissue enzyme comparisons. · source_derived_draft · unverified_draft

    ## isoleucine-echs1-boundary A pathway diagram alone can overstate an enzyme as an unavoidable gate. ECHS1-deficient patients showed a dominant valine-metabolism defect rather than the expected isolated isoleucine block; liver retained tiglyl-CoA hydration capacity. Model: Four-patient biochemical study with tissue enzyme comparisons. Limitations: Does not establish the same backup capacity in every cell type. Evidence access: Primary full text 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

  11. BAT-specific Slc25a44 deletion blunted BCAA oxidation and non-shivering thermogenesis following intracerebroventricular PGE2.

    Mouse mitochondrial BCAA carrier / Slc25a44 → PGE2-evoked BAT thermogenesis in mice source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Mouse conditional knockout; PGE2 1.4 micrograms per mouse; valine oxidation readout.
    limitations
    Not an isoleucine-specific tracer result or a supplement treatment for fever.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    The shared mitochondrial gate mattered during a defined fever response.
    primary_references
    Metabolic flexibility via mitochondrial BCAA carrier SLC25A44 is required for optimal fever. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33944778/ · DOI 10.7554/eLife.66865
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 74–80

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse conditional knockout; PGE2 1.4 micrograms per mouse; valine oxidation readout. · source_derived_draft · unverified_draft

    ## isoleucine-fever-carrier The shared mitochondrial gate mattered during a defined fever response. BAT-specific Slc25a44 deletion blunted BCAA oxidation and non-shivering thermogenesis following intracerebroventricular PGE2. Model: Mouse conditional knockout; PGE2 1.4 micrograms per mouse; valine oxidation readout. Limitations: Not an isoleucine-specific tracer result or a supplement treatment for fever. Evidence access: Primary full text Metabolic flexibility via mitochondrial BCAA carrier SLC25A44 is required for optimal fever. · 2021 · https://pubmed.ncbi.nlm.nih.gov/33944778/ · DOI 10.7554/eLife.66865
    Complete structured claim and evidence

  12. Slc25a44 loss reduced mitochondrial valine and leucine uptake; ectopic expression and reconstituted liposomes supported transporter function.

    Mouse mitochondrial BCAA carrier / Slc25a44 → Mitochondrial BCAA uptake in mouse cells source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary full text
    experimental_model
    Mouse brown adipocytes/Neuro2a and membrane/proteoliposome assays.
    limitations
    Direct transport tracers highlighted here were valine and leucine; do not relabel them as an isolated isoleucine transport assay.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    Access to mitochondria is a separate gate from entry into the cell.
    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
    transport_effect
    raises The object already names mitochondrial BCAA uptake.
    transport_pool
    the mitochondrial matrix The object already names mitochondrial BCAA uptake.

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 50–56

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse brown adipocytes/Neuro2a and membrane/proteoliposome assays. · source_derived_draft · unverified_draft

    ## isoleucine-mitochondrial-carrier Access to mitochondria is a separate gate from entry into the cell. Slc25a44 loss reduced mitochondrial valine and leucine uptake; ectopic expression and reconstituted liposomes supported transporter function. Model: Mouse brown adipocytes/Neuro2a and membrane/proteoliposome assays. Limitations: Direct transport tracers highlighted here were valine and leucine; do not relabel them as an isolated isoleucine transport assay. 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

  13. Phenylbutyrate reduced BCAA/BCKA pools in controls and some late-onset/intermediate MSUD patients; cultured-cell responses did not simply predict the clinical biochemical response.

    Sodium phenylbutyrate → BCAA and branched-ketoacid pools in selected MSUD patients source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Small human treatment study plus patient-cell assays.
    limitations
    Not universal MSUD efficacy or long-term outcome evidence.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    The same drug interaction can help or deplete depending on the disease and remaining enzyme function.
    primary_references
    Phenylbutyrate therapy for maple syrup urine disease. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21098507/ · DOI 10.1093/hmg/ddq507
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 314–320

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Small human treatment study plus patient-cell assays. · source_derived_draft · unverified_draft

    ## isoleucine-msud-drug-response The same drug interaction can help or deplete depending on the disease and remaining enzyme function. Phenylbutyrate reduced BCAA/BCKA pools in controls and some late-onset/intermediate MSUD patients; cultured-cell responses did not simply predict the clinical biochemical response. Model: Small human treatment study plus patient-cell assays. Limitations: Not universal MSUD efficacy or long-term outcome evidence. Evidence access: Primary abstract Phenylbutyrate therapy for maple syrup urine disease. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21098507/ · DOI 10.1093/hmg/ddq507
    Complete structured claim and evidence

  14. In the preprint, propionate rescued propionyl-CoA and selected histone propionylation after combined isoleucine/valine deprivation, but did not restore proliferation.

    Propionate → Histone propionylation in PDA cell models source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    evidence_access
    Primary preprint full text; not peer reviewed
    experimental_model
    Mouse KPC and human PDA cell assays; combined Ile/Val removal, twenty-four hours.
    limitations
    Preprint; deprivation of two amino acids cannot be attributed exclusively to one.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    Restoring one carbon product did not replace essential amino-acid supply.
    primary_references
    A nuclear branched-chain amino acid catabolism pathway controls histone propionylation in pancreatic cancer. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40568091/ · DOI 10.1101/2025.04.23.650241
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 482–488

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse KPC and human PDA cell assays; combined Ile/Val removal, twenty-four hours. · source_derived_draft · unverified_draft

    ## isoleucine-pancreatic-preprint-rescue Restoring one carbon product did not replace essential amino-acid supply. In the preprint, propionate rescued propionyl-CoA and selected histone propionylation after combined isoleucine/valine deprivation, but did not restore proliferation. Model: Mouse KPC and human PDA cell assays; combined Ile/Val removal, twenty-four hours. Limitations: Preprint; deprivation of two amino acids cannot be attributed exclusively to one. Evidence access: Primary preprint full text; not peer reviewed A nuclear branched-chain amino acid catabolism pathway controls histone propionylation in pancreatic cancer. · 2025 · https://pubmed.ncbi.nlm.nih.gov/40568091/ · DOI 10.1101/2025.04.23.650241
    Complete structured claim and evidence

  15. Phenylbutyrate inhibited recombinant BCKDH kinase, reduced E1-alpha phosphorylation and increased overall BCKDH activity in the reported assays.

    Sodium phenylbutyrate → Recombinant BCKDH-kinase preparation, species unresolved in accessed abstract source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Recombinant enzyme assays with supporting cellular/in-vivo experiments.
    limitations
    Protein species is not inferred from the patient part of the paper; activity responses varied among disease samples.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    A medicine can remove the brake on BCAA breakdown.
    primary_references
    Phenylbutyrate therapy for maple syrup urine disease. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21098507/ · DOI 10.1093/hmg/ddq507

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 298–304

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Recombinant enzyme assays with supporting cellular/in-vivo experiments. · source_derived_draft · unverified_draft

    ## isoleucine-phenylbutyrate-kinase A medicine can remove the brake on BCAA breakdown. Phenylbutyrate inhibited recombinant BCKDH kinase, reduced E1-alpha phosphorylation and increased overall BCKDH activity in the reported assays. Model: Recombinant enzyme assays with supporting cellular/in-vivo experiments. Limitations: Protein species is not inferred from the patient part of the paper; activity responses varied among disease samples. Evidence access: Primary abstract Phenylbutyrate therapy for maple syrup urine disease. · 2011 · https://pubmed.ncbi.nlm.nih.gov/21098507/ · DOI 10.1093/hmg/ddq507
    Complete structured claim and evidence

  16. Sodium phenylbutyrate-treated urea-cycle-disorder patients had lower circulating BCAAs despite adequate protein intake; low steady-state BCAAs were also observed in treated controls.

    Sodium phenylbutyrate → Circulating BCAAs during sodium phenylbutyrate exposure source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    biomarker_context Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Human stable-isotope-study sampling and treated control comparisons.
    limitations
    Mixed BCAA effect; dietary decisions in urea-cycle disorders require the full clinical context.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    A low amino-acid pool can reflect drug-related handling, not just low intake.
    primary_references
    New insights in nutritional management and amino acid supplementation in urea cycle disorders. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20299258/ · DOI 10.1016/j.ymgme.2010.02.019
    trigger_kind
    biomarker_context Imported condition classification; unverified.

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 306–312

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Human stable-isotope-study sampling and treated control comparisons. · source_derived_draft · unverified_draft

    ## isoleucine-phenylbutyrate-plasma A low amino-acid pool can reflect drug-related handling, not just low intake. Sodium phenylbutyrate-treated urea-cycle-disorder patients had lower circulating BCAAs despite adequate protein intake; low steady-state BCAAs were also observed in treated controls. Model: Human stable-isotope-study sampling and treated control comparisons. Limitations: Mixed BCAA effect; dietary decisions in urea-cycle disorders require the full clinical context. Evidence access: Primary abstract New insights in nutritional management and amino acid supplementation in urea cycle disorders. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20299258/ · DOI 10.1016/j.ymgme.2010.02.019
    Complete structured claim and evidence

  17. PP2Cm bound the BCKDH complex and promoted substrate-dependent dephosphorylation of E1-alpha Ser293.

    Mouse BCKDH phosphatase PP2Cm / Ppm1k → Mouse branched-chain alpha-ketoacid dehydrogenase complex source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Mouse and cultured-cell protein interaction/phosphorylation experiments.
    limitations
    Rate depends on substrate and regulatory state; this is a shared BCAA step.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    A phosphatase removes the inhibitory mark and permits more breakdown.
    primary_references
    Protein phosphatase 2Cm is a critical regulator of branched-chain amino acid catabolism in mice and cultured cells. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19411760/ · DOI 10.1172/JCI38151

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 274–280

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Mouse and cultured-cell protein interaction/phosphorylation experiments. · source_derived_draft · unverified_draft

    ## isoleucine-ppm1k-activation A phosphatase removes the inhibitory mark and permits more breakdown. PP2Cm bound the BCKDH complex and promoted substrate-dependent dephosphorylation of E1-alpha Ser293. Model: Mouse and cultured-cell protein interaction/phosphorylation experiments. Limitations: Rate depends on substrate and regulatory state; this is a shared BCAA step. Evidence access: Primary abstract Protein phosphatase 2Cm is a critical regulator of branched-chain amino acid catabolism in mice and cultured cells. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19411760/ · DOI 10.1172/JCI38151
    Complete structured claim and evidence

  18. Ppm1k loss abolished substrate-induced E1-alpha dephosphorylation and impaired BCAA catabolism in mice.

    Mouse BCKDH phosphatase PP2Cm / Ppm1k → Substrate-induced BCKDH activation in mice source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_access
    Primary abstract
    experimental_model
    Ppm1k-deficient mice and cultured cells.
    limitations
    Mouse MSUD-like phenotype is not a diagnosis of dietary BCAA excess.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    Failure to release the brake can produce accumulation rather than shortage.
    primary_references
    Protein phosphatase 2Cm is a critical regulator of branched-chain amino acid catabolism in mice and cultured cells. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19411760/ · DOI 10.1172/JCI38151
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 282–288

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Ppm1k-deficient mice and cultured cells. · source_derived_draft · unverified_draft

    ## isoleucine-ppm1k-loss Failure to release the brake can produce accumulation rather than shortage. Ppm1k loss abolished substrate-induced E1-alpha dephosphorylation and impaired BCAA catabolism in mice. Model: Ppm1k-deficient mice and cultured cells. Limitations: Mouse MSUD-like phenotype is not a diagnosis of dietary BCAA excess. Evidence access: Primary abstract Protein phosphatase 2Cm is a critical regulator of branched-chain amino acid catabolism in mice and cultured cells. · 2009 · https://pubmed.ncbi.nlm.nih.gov/19411760/ · DOI 10.1172/JCI38151
    Complete structured claim and evidence

  19. A 2026 prostate-cancer study identified isoleucine and valine catabolism as major sources of intracellular propionyl-CoA in its experimental models.

    L-Isoleucine → Propionyl-CoA source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Prostate-cancer cell and tumor models; detailed species/exposure unresolved in accessed abstract.
    limitations
    Not proof that dietary intake causes prostate cancer or that restriction treats patients.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    Two amino-acid branches converged on the same signaling metabolite.
    primary_references
    Isoleucine and valine promote prostate cancer progression via propionyl-CoA-mediated cholesterol metabolism. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42625032/ · DOI 10.1038/s42255-026-01583-z

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 498–504

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Prostate-cancer cell and tumor models; detailed species/exposure unresolved in accessed abstract. · source_derived_draft · unverified_draft

    ## isoleucine-prostate-carbon Two amino-acid branches converged on the same signaling metabolite. A 2026 prostate-cancer study identified isoleucine and valine catabolism as major sources of intracellular propionyl-CoA in its experimental models. Model: Prostate-cancer cell and tumor models; detailed species/exposure unresolved in accessed abstract. Limitations: Not proof that dietary intake causes prostate cancer or that restriction treats patients. Evidence access: Primary abstract Isoleucine and valine promote prostate cancer progression via propionyl-CoA-mediated cholesterol metabolism. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42625032/ · DOI 10.1038/s42255-026-01583-z
    Complete structured claim and evidence

  20. The reported SREBP2 activation promoted cholesterol biosynthesis and supported de novo androgen production and androgen-receptor signaling under metabolic/androgen-deprivation stress.

    SREBP2 in the prostate-cancer study, species unresolved here → Cholesterol synthesis and androgen signaling in prostate-cancer models source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Prostate-cancer experimental models.
    limitations
    Does not imply a testosterone-boosting effect of supplements or a human dietary cancer treatment.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    The pathway linked amino-acid carbon handling to lipid and hormone-related tumor adaptation.
    primary_references
    Isoleucine and valine promote prostate cancer progression via propionyl-CoA-mediated cholesterol metabolism. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42625032/ · DOI 10.1038/s42255-026-01583-z

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 514–520

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Prostate-cancer experimental models. · source_derived_draft · unverified_draft

    ## isoleucine-prostate-cholesterol The pathway linked amino-acid carbon handling to lipid and hormone-related tumor adaptation. The reported SREBP2 activation promoted cholesterol biosynthesis and supported de novo androgen production and androgen-receptor signaling under metabolic/androgen-deprivation stress. Model: Prostate-cancer experimental models. Limitations: Does not imply a testosterone-boosting effect of supplements or a human dietary cancer treatment. Evidence access: Primary abstract Isoleucine and valine promote prostate cancer progression via propionyl-CoA-mediated cholesterol metabolism. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42625032/ · DOI 10.1038/s42255-026-01583-z
    Complete structured claim and evidence

  21. Propionyl-CoA-dependent site-specific lysine propionylation stabilized nuclear SREBP2 and increased its transcriptional activity in the reported prostate-cancer models.

    Propionyl-CoA → SREBP2 in the prostate-cancer study, species unresolved here source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Primary prostate-cancer mechanistic study; exact construct and lysine site not resolved in accessed abstract.
    limitations
    Site identity is not guessed; clinical target engagement was not established.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    A breakdown product changed the stability of a lipid-regulating transcription factor.
    primary_references
    Isoleucine and valine promote prostate cancer progression via propionyl-CoA-mediated cholesterol metabolism. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42625032/ · DOI 10.1038/s42255-026-01583-z

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 506–512

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary prostate-cancer mechanistic study; exact construct and lysine site not resolved in accessed abstract. · source_derived_draft · unverified_draft

    ## isoleucine-prostate-srebp2 A breakdown product changed the stability of a lipid-regulating transcription factor. Propionyl-CoA-dependent site-specific lysine propionylation stabilized nuclear SREBP2 and increased its transcriptional activity in the reported prostate-cancer models. Model: Primary prostate-cancer mechanistic study; exact construct and lysine site not resolved in accessed abstract. Limitations: Site identity is not guessed; clinical target engagement was not established. Evidence access: Primary abstract Isoleucine and valine promote prostate cancer progression via propionyl-CoA-mediated cholesterol metabolism. · 2026 · https://pubmed.ncbi.nlm.nih.gov/42625032/ · DOI 10.1038/s42255-026-01583-z
    Complete structured claim and evidence

  22. Under isoleucine restriction, healthy human fibroblasts incorporated valine at isoleucine codons; biochemical assays implicated IARS1-mediated valine misacylation.

    Human cytosolic isoleucyl-tRNA synthetase / IARS1 → Isoleucine-to-valine protein substitution in human fibroblasts source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    evidence_access
    Primary full text
    experimental_model
    Primary human fibroblasts, mass spectrometry and tRNA charging assays.
    limitations
    Amino-acid substitution is not proof of normal function for every affected protein or nutritional interchangeability.
    nutrient_topic
    L-Isoleucine collection; species, compartment, exposure, co-substrates and manipulation remain explicit. · L-Isoleucine
    plain_language
    Some cells preserve translation by sacrificing amino-acid accuracy.
    primary_references
    Isoleucine-to-valine substitutions support cellular physiology during isoleucine deprivation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39657787/ · DOI 10.1093/nar/gkae1184
    trigger_kind
    nutrient_deficiency Imported condition classification; unverified.

    L-Isoleucine: transport, translation, catabolism and cross-nutrient mechanisms (2026-09-19) · lines 114–120

    AI-assisted research curation; primary references, access levels and experimental limitations individually identified. Not publisher full text. · supports · Primary human fibroblasts, mass spectrometry and tRNA charging assays. · source_derived_draft · unverified_draft

    ## isoleucine-valine-substitution Some cells preserve translation by sacrificing amino-acid accuracy. Under isoleucine restriction, healthy human fibroblasts incorporated valine at isoleucine codons; biochemical assays implicated IARS1-mediated valine misacylation. Model: Primary human fibroblasts, mass spectrometry and tRNA charging assays. Limitations: Amino-acid substitution is not proof of normal function for every affected protein or nutritional interchangeability. Evidence access: Primary full text Isoleucine-to-valine substitutions support cellular physiology during isoleucine deprivation. · 2025 · https://pubmed.ncbi.nlm.nih.gov/39657787/ · DOI 10.1093/nar/gkae1184
    Complete structured claim and evidence

  23. 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

  24. Four-week thiamine-deprived rats had mean total plasma branched-chain amino acids 1.6 times control.

    Thiamine (vitamin B1) → Plasma total branched-chain amino-acid concentration source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    nutrient_deficiency Imported condition classification; unverified.
    cross_nutrient
    Dietary B1 deprivation perturbed branched-chain amino-acid metabolism.
    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
    Severe animal depletion; not a plasma B1 diagnostic cutoff.
    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
    Severe dietary B1 deprivation altered the circulating pool of leucine, isoleucine and valine in this rat experiment.
    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 814–826

    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-bcaa-rise Four-week thiamine-deprived rats had mean total plasma branched-chain amino acids 1.6 times control. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Severe dietary B1 deprivation altered the circulating pool of leucine, isoleucine and valine in this rat experiment. organism: Rattus norvegicus tissue_or_cell_type: Plasma; liver thiamine measured experimental_model: Four-week dietary depletion. limitations: Severe animal depletion; not a plasma B1 diagnostic cutoff. 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: Dietary B1 deprivation perturbed branched-chain amino-acid metabolism. 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.

    Evidence, AI assistance and curation standards