Component

Human pyruvate dehydrogenase E1

PDHA1/PDHB alpha2-beta2 enzyme; distinct from the full PDH complex.

6 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. Recombinant human E1 transferred radiolabel from pyruvate to the lipoylated DLAT L2 domain, directly measuring reductive acetylation.

    Human pyruvate dehydrogenase E1 → Dihydrolipoyl acetyltransferase / DLAT source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Thiamine-dependent carbon chemistry requires the separate protein-bound lipoyl carrier; free lipoic-acid supplementation was not tested.
    evidence
    [{"paper_key": "kato-2008-pdh-phosphorylation", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-19", "p-25"], "locator": "incorporation", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
    experimental_model
    Human recombinant proteins; radiolabeled pyruvate assay.
    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
    The B1-dependent enzyme passes pyruvate-derived carbon to a lipoyl arm on a different protein. Protein-bound lipoate therefore links E1 chemistry to the next reaction.
    primary_references
    [kato-2008-pdh-phosphorylation] Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops (2008). https://pubmed.ncbi.nlm.nih.gov/19081061/ DOI: 10.1016/j.str.2008.10.010
    tissue_or_cell_type
    Purified proteins

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 676–688

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

    ### b1-pdh-lipoyl-acetyl-transfer Recombinant human E1 transferred radiolabel from pyruvate to the lipoylated DLAT L2 domain, directly measuring reductive acetylation. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The B1-dependent enzyme passes pyruvate-derived carbon to a lipoyl arm on a different protein. Protein-bound lipoate therefore links E1 chemistry to the next reaction. organism: Homo sapiens tissue_or_cell_type: Purified proteins experimental_model: Human recombinant proteins; radiolabeled pyruvate assay. limitations: Purified-system evidence; nutritional response was not tested. evidence: [{"paper_key": "kato-2008-pdh-phosphorylation", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-19", "p-25"], "locator": "incorporation", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: Thiamine-dependent carbon chemistry requires the separate protein-bound lipoyl carrier; free lipoic-acid supplementation was not tested. nutrient: Thiamine (vitamin B1) [kato-2008-pdh-phosphorylation] Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops (2008). https://pubmed.ncbi.nlm.nih.gov/19081061/ DOI: 10.1016/j.str.2008.10.010
    Complete structured claim and evidence

  2. Human PDH E1 forms a covalent lactyl-ThDP intermediate from pyruvate and decarboxylates it, retaining the two-carbon fragment on ThDP.

    Human pyruvate dehydrogenase E1 → Pyruvate source_derived_draftungraded
    Experimental context and source evidence
    evidence
    [{"paper_key": "seifert-2006-pdh-catalysis", "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 E1; transient kinetics.
    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
    Activated vitamin B1 temporarily holds pyruvate while one carbon leaves as carbon dioxide. This is the first reaction, before acetyl-CoA is made.
    primary_references
    [seifert-2006-pdh-catalysis] Direct kinetic evidence for half-of-the-sites reactivity in the E1 component of the human pyruvate dehydrogenase multienzyme complex through alternating sites cofactor activation (2006). https://pubmed.ncbi.nlm.nih.gov/17042496/ DOI: 10.1021/bi061582l
    tissue_or_cell_type
    Purified mitochondrial enzyme

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 663–674

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human E1; transient kinetics. · source_derived_draft · unverified_draft

    ### b1-pdh-pyruvate-covalent-decarboxylation Human PDH E1 forms a covalent lactyl-ThDP intermediate from pyruvate and decarboxylates it, retaining the two-carbon fragment on ThDP. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Activated vitamin B1 temporarily holds pyruvate while one carbon leaves as carbon dioxide. This is the first reaction, before acetyl-CoA is made. organism: Homo sapiens tissue_or_cell_type: Purified mitochondrial enzyme experimental_model: Recombinant human E1; transient kinetics. limitations: Purified-system evidence; nutritional response was not tested. evidence: [{"paper_key": "seifert-2006-pdh-catalysis", "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) [seifert-2006-pdh-catalysis] Direct kinetic evidence for half-of-the-sites reactivity in the E1 component of the human pyruvate dehydrogenase multienzyme complex through alternating sites cofactor activation (2006). https://pubmed.ncbi.nlm.nih.gov/17042496/ DOI: 10.1021/bi061582l
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Wild-type human PDH E1 structures show Mg coordinated at the ThDP diphosphate-binding site.

    Mg2+ → Thiamine diphosphate source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply.
    experimental_model
    Recombinant human wild-type and alphaV138M E1 structures and reconstituted PDH complex activity.
    limitations
    Structure supports binding geometry; no magnesium-deficiency intervention was performed.
    nutrient_topic
    Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
    organism
    Homo sapiens
    plain_language
    Magnesium helps position the B1-derived cofactor in the pyruvate-processing enzyme.
    primary_references
    [whitley-2018-pdh] Pyruvate dehydrogenase complex deficiency is linked to regulatory loop disorder in the αV138M variant of human pyruvate dehydrogenase (2018). https://pmc.ncbi.nlm.nih.gov/articles/PMC6109939/ DOI: 10.1074/jbc.RA118.003996
    tissue_or_cell_type
    Recombinant mitochondrial enzyme

    Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 613–623

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human wild-type and alphaV138M E1 structures and reconstituted PDH complex activity. · source_derived_draft · unverified_draft

    ### mg-pdh-e1-thdp-anchor Wild-type human PDH E1 structures show Mg coordinated at the ThDP diphosphate-binding site. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium helps position the B1-derived cofactor in the pyruvate-processing enzyme. organism: Homo sapiens tissue_or_cell_type: Recombinant mitochondrial enzyme experimental_model: Recombinant human wild-type and alphaV138M E1 structures and reconstituted PDH complex activity. limitations: Structure supports binding geometry; no magnesium-deficiency intervention was performed. cross_nutrient: Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply. [whitley-2018-pdh] Pyruvate dehydrogenase complex deficiency is linked to regulatory loop disorder in the αV138M variant of human pyruvate dehydrogenase (2018). https://pmc.ncbi.nlm.nih.gov/articles/PMC6109939/ DOI: 10.1074/jbc.RA118.003996
    Complete structured claim and evidence

  2. The alphaV138M E1 structure displaced ThDP and disrupted the canonical Mg coordination site.

    Human pyruvate dehydrogenase E1 alphaV138M variant → Mg2+ source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply.
    experimental_model
    Recombinant human wild-type and alphaV138M E1 structures and reconstituted PDH complex activity.
    limitations
    The variant also alters loop structure; Mg loss alone was not isolated as the cause.
    nutrient_topic
    Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
    organism
    Homo sapiens
    plain_language
    An altered protein can impair cofactor use despite cofactors being supplied.
    primary_references
    [whitley-2018-pdh] Pyruvate dehydrogenase complex deficiency is linked to regulatory loop disorder in the αV138M variant of human pyruvate dehydrogenase (2018). https://pmc.ncbi.nlm.nih.gov/articles/PMC6109939/ DOI: 10.1074/jbc.RA118.003996
    tissue_or_cell_type
    Recombinant mitochondrial enzyme
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 625–635

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human wild-type and alphaV138M E1 structures and reconstituted PDH complex activity. · source_derived_draft · unverified_draft

    ### mg-pdh-variant-disrupts-coordination The alphaV138M E1 structure displaced ThDP and disrupted the canonical Mg coordination site. Condition category: machinery_impairment nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: An altered protein can impair cofactor use despite cofactors being supplied. organism: Homo sapiens tissue_or_cell_type: Recombinant mitochondrial enzyme experimental_model: Recombinant human wild-type and alphaV138M E1 structures and reconstituted PDH complex activity. limitations: The variant also alters loop structure; Mg loss alone was not isolated as the cause. cross_nutrient: Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply. [whitley-2018-pdh] Pyruvate dehydrogenase complex deficiency is linked to regulatory loop disorder in the αV138M variant of human pyruvate dehydrogenase (2018). https://pmc.ncbi.nlm.nih.gov/articles/PMC6109939/ DOI: 10.1074/jbc.RA118.003996
    Complete structured claim and evidence

  3. Phosphorylated human site-1-only E1 lacked detectable lipoylated-L2 binding and reductive acetylation, despite high ThDP in the binding assay.

    PDH E1 phosphorylated at alpha Ser264 → Dihydrolipoyl acetyltransferase / DLAT source_derived_draftungraded
    Experimental context and source evidence
    evidence
    [{"paper_key": "kato-2008-pdh-phosphorylation", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-51"], "locator": "absence of L2 binding", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
    experimental_model
    Engineered human site-1-only E1; phosphorylation, ITC and kinetics.
    limitations
    Normal regulatory phosphorylation studied in an engineered construct; not a dietary deficiency or clinical nonresponse experiment.
    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
    Loading B1 cannot by itself undo this tested regulatory block: the phosphorylated enzyme fails to engage its lipoyl partner.
    primary_references
    [kato-2008-pdh-phosphorylation] Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops (2008). https://pubmed.ncbi.nlm.nih.gov/19081061/ DOI: 10.1016/j.str.2008.10.010
    tissue_or_cell_type
    Purified proteins

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 704–715

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Engineered human site-1-only E1; phosphorylation, ITC and kinetics. · source_derived_draft · unverified_draft

    ### b1-pdh-phosphorylation-blocks-lipoyl-recognition Phosphorylated human site-1-only E1 lacked detectable lipoylated-L2 binding and reductive acetylation, despite high ThDP in the binding assay. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Loading B1 cannot by itself undo this tested regulatory block: the phosphorylated enzyme fails to engage its lipoyl partner. organism: Homo sapiens tissue_or_cell_type: Purified proteins experimental_model: Engineered human site-1-only E1; phosphorylation, ITC and kinetics. limitations: Normal regulatory phosphorylation studied in an engineered construct; not a dietary deficiency or clinical nonresponse experiment. evidence: [{"paper_key": "kato-2008-pdh-phosphorylation", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-51"], "locator": "absence of L2 binding", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] nutrient: Thiamine (vitamin B1) [kato-2008-pdh-phosphorylation] Structural basis for inactivation of the human pyruvate dehydrogenase complex by phosphorylation: role of disordered phosphorylation loops (2008). https://pubmed.ncbi.nlm.nih.gov/19081061/ DOI: 10.1016/j.str.2008.10.010
    Complete structured claim and evidence

  4. Patient muscle PDH activity was deficient without added ThDP but normal or near-normal under cofactor-supplemented assay conditions.

    Thiamine diphosphate → Pyruvate dehydrogenase complex activity source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence-scope
    Muscle and blood
    evidence_locator
    Figure 3; Table 1
    evidence_spans
    [{"source_document": "artifacts/thiamine_transport_sources/PMC3234371.txt", "start_char": 12774, "end_char": 13380}]
    experimental_model
    Five patients from three families; muscle/blood chemistry and enzyme assays.
    limitations
    Ex vivo cofactor rescue does not establish oral ThDP delivery or clinical efficacy.
    nutrient_topic
    Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
    organism
    Homo sapiens
    plain_language
    Supplying cofactor directly to the assay exposed an activation problem upstream of PDH.
    primary_references
    [mayr-2011-tpk1-deficiency] Thiamine pyrophosphokinase deficiency in encephalopathic children with defects in the pyruvate oxidation pathway (2011). https://pmc.ncbi.nlm.nih.gov/articles/PMC3234371/ DOI: 10.1016/j.ajhg.2011.11.007
    tissue_or_cell_type
    Muscle and blood
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 402–414

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Five patients from three families; muscle/blood chemistry and enzyme assays. · source_derived_draft · unverified_draft

    ### b1-tpk1-deficiency-pdh-assay-rescue Patient muscle PDH activity was deficient without added ThDP but normal or near-normal under cofactor-supplemented assay conditions. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Supplying cofactor directly to the assay exposed an activation problem upstream of PDH. organism: Homo sapiens tissue_or_cell_type: Muscle and blood experimental_model: Five patients from three families; muscle/blood chemistry and enzyme assays. limitations: Ex vivo cofactor rescue does not establish oral ThDP delivery or clinical efficacy. evidence_locator: Figure 3; Table 1 evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/PMC3234371.txt", "start_char": 12774, "end_char": 13380}] evidence-scope: Muscle and blood [mayr-2011-tpk1-deficiency] Thiamine pyrophosphokinase deficiency in encephalopathic children with defects in the pyruvate oxidation pathway (2011). https://pmc.ncbi.nlm.nih.gov/articles/PMC3234371/ DOI: 10.1016/j.ajhg.2011.11.007
    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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