Component

Human thiamine pyrophosphokinase 1

Human TPK1 catalyzes thiamine diphosphate synthesis.

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 acts on it

  1. Mg2+ in excess over ATP restored human TPK1 activity at low MgATP concentrations compared with a 1:1 total Mg:ATP ratio.

    Mg2+ → Human thiamine pyrophosphokinase 1 source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure.
    experimental_model
    Purified His-tagged recombinant human TPK1, steady-state kinetics and mutations.
    limitations
    Total concentrations and speciation must be distinguished; no human Mg cutoff follows.
    nutrient_topic
    Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
    organism
    Homo sapiens
    plain_language
    The balance between ATP-bound and available magnesium affects activation of B1.
    primary_references
    [onozuka-2003-tpk1] Steady-state kinetics and mutational studies of recombinant human thiamin pyrophosphokinase (2003). https://pubmed.ncbi.nlm.nih.gov/12953792/ DOI: 10.3177/jnsv.49.156
    tissue_or_cell_type
    Purified recombinant enzyme

    Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 493–503

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified His-tagged recombinant human TPK1, steady-state kinetics and mutations. · source_derived_draft · unverified_draft

    ### mg-tpk1-free-mg-restores-activity Mg2+ in excess over ATP restored human TPK1 activity at low MgATP concentrations compared with a 1:1 total Mg:ATP ratio. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The balance between ATP-bound and available magnesium affects activation of B1. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme experimental_model: Purified His-tagged recombinant human TPK1, steady-state kinetics and mutations. limitations: Total concentrations and speciation must be distinguished; no human Mg cutoff follows. cross_nutrient: Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure. [onozuka-2003-tpk1] Steady-state kinetics and mutational studies of recombinant human thiamin pyrophosphokinase (2003). https://pubmed.ncbi.nlm.nih.gov/12953792/ DOI: 10.3177/jnsv.49.156
    Complete structured claim and evidence

  2. D71N markedly decreased recombinant human TPK1 catalytic turnover.

    Human TPK1 D71N experimental variant → Human thiamine pyrophosphokinase 1 source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence-scope
    Recombinant enzyme
    evidence_locator
    Abstract
    evidence_spans
    [{"source_document": "artifacts/thiamine_transport_sources/onozuka-2003-tpk1-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1438}]
    experimental_model
    Purified His-tagged human TPK1; ATP/Mg kinetics and mutagenesis.
    limitations
    Engineered mutation; not an isolated clinical magnesium effect.
    nutrient_topic
    Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
    organism
    Homo sapiens
    plain_language
    Disrupting an active-site residue impairs B1 activation.
    primary_references
    [onozuka-2003-tpk1] Steady-state kinetics and mutational studies of recombinant human thiamin pyrophosphokinase (2003). https://pubmed.ncbi.nlm.nih.gov/12953792/ DOI: 10.3177/jnsv.49.156 [sambon-2022-tpk1] Product inhibition of mammalian thiamine pyrophosphokinase is an important mechanism for maintaining thiamine diphosphate homeostasis (2022). https://doi.org/10.1016/j.bbagen.2021.130071 DOI: 10.1016/j.bbagen.2021.130071
    tissue_or_cell_type
    Recombinant enzyme
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 358–371

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified His-tagged human TPK1; ATP/Mg kinetics and mutagenesis. · source_derived_draft · unverified_draft

    ### b1-tpk1-d71n-catalysis D71N markedly decreased recombinant human TPK1 catalytic turnover. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Disrupting an active-site residue impairs B1 activation. organism: Homo sapiens tissue_or_cell_type: Recombinant enzyme experimental_model: Purified His-tagged human TPK1; ATP/Mg kinetics and mutagenesis. limitations: Engineered mutation; not an isolated clinical magnesium effect. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/onozuka-2003-tpk1-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1438}] evidence_locator: Abstract evidence-scope: Recombinant enzyme [onozuka-2003-tpk1] Steady-state kinetics and mutational studies of recombinant human thiamin pyrophosphokinase (2003). https://pubmed.ncbi.nlm.nih.gov/12953792/ DOI: 10.3177/jnsv.49.156 [sambon-2022-tpk1] Product inhibition of mammalian thiamine pyrophosphokinase is an important mechanism for maintaining thiamine diphosphate homeostasis (2022). https://doi.org/10.1016/j.bbagen.2021.130071 DOI: 10.1016/j.bbagen.2021.130071
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Recombinant human TPK1 catalyzes thiamine diphosphorylation with ATP and Mg2+.

    Thiamine (vitamin B1) → Thiamine diphosphate source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure.
    experimental_model
    Purified His-tagged recombinant human TPK1, steady-state kinetics and mutations.
    limitations
    Assay chemistry; no clinical response measured.
    nutrient_topic
    Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium
    organism
    Homo sapiens
    plain_language
    The enzyme uses ATP to convert vitamin B1 into its diphosphate cofactor.
    primary_references
    [onozuka-2003-tpk1] Steady-state kinetics and mutational studies of recombinant human thiamin pyrophosphokinase (2003). https://pubmed.ncbi.nlm.nih.gov/12953792/ DOI: 10.3177/jnsv.49.156
    tissue_or_cell_type
    Purified recombinant enzyme

    Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 481–491

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified His-tagged recombinant human TPK1, steady-state kinetics and mutations. · source_derived_draft · unverified_draft

    ### mg-tpk1-thiamine-to-thdp Recombinant human TPK1 catalyzes thiamine diphosphorylation with ATP and Mg2+. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme uses ATP to convert vitamin B1 into its diphosphate cofactor. organism: Homo sapiens tissue_or_cell_type: Purified recombinant enzyme experimental_model: Purified His-tagged recombinant human TPK1, steady-state kinetics and mutations. limitations: Assay chemistry; no clinical response measured. cross_nutrient: Magnesium availability supports vitamin B1 activation or cofactor use in the specified preparation; this does not establish a dietary threshold or universal treatment failure. [onozuka-2003-tpk1] Steady-state kinetics and mutational studies of recombinant human thiamin pyrophosphokinase (2003). https://pubmed.ncbi.nlm.nih.gov/12953792/ DOI: 10.3177/jnsv.49.156
    Complete structured claim and evidence

  2. TPK1 activation transfers ATP-derived diphosphoryl to thiamine, yielding ThDP and AMP in a magnesium-dependent reaction.

    ATP → Thiamine (vitamin B1) source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    Mg-dependent ATP chemistry activates B1; it does not imply every later ThDP-binding event consumes ATP.
    curation_note
    Adds explicit phosphate-transfer/AMP-product detail to the existing magnesium collection.
    evidence-scope
    Recombinant enzyme
    evidence_locator
    Abstract
    evidence_spans
    [{"source_document": "artifacts/thiamine_transport_sources/sambon-2022-tpk1-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1689}]
    experimental_model
    Purified His-tagged human TPK1; ATP/Mg kinetics and mutagenesis.
    limitations
    Overall chemistry does not resolve substrate-binding order.
    nutrient_topic
    Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
    organism
    Homo sapiens
    plain_language
    B1 activation uses ATP and releases AMP; it is not an ATP-to-ADP single-phosphate step.
    primary_references
    [onozuka-2003-tpk1] Steady-state kinetics and mutational studies of recombinant human thiamin pyrophosphokinase (2003). https://pubmed.ncbi.nlm.nih.gov/12953792/ DOI: 10.3177/jnsv.49.156 [sambon-2022-tpk1] Product inhibition of mammalian thiamine pyrophosphokinase is an important mechanism for maintaining thiamine diphosphate homeostasis (2022). https://doi.org/10.1016/j.bbagen.2021.130071 DOI: 10.1016/j.bbagen.2021.130071
    reaction
    thiamine + ATP -> thiamine diphosphate + AMP
    related_existing_claim_keys
    ["mg-tpk1-thiamine-to-thdp"]
    tissue_or_cell_type
    Recombinant enzyme

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 339–356

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified His-tagged human TPK1; ATP/Mg kinetics and mutagenesis. · source_derived_draft · unverified_draft

    ### b1-tpk1-atp-amp-stoichiometry TPK1 activation transfers ATP-derived diphosphoryl to thiamine, yielding ThDP and AMP in a magnesium-dependent reaction. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 activation uses ATP and releases AMP; it is not an ATP-to-ADP single-phosphate step. organism: Homo sapiens tissue_or_cell_type: Recombinant enzyme experimental_model: Purified His-tagged human TPK1; ATP/Mg kinetics and mutagenesis. limitations: Overall chemistry does not resolve substrate-binding order. cross_nutrient: Mg-dependent ATP chemistry activates B1; it does not imply every later ThDP-binding event consumes ATP. reaction: thiamine + ATP -> thiamine diphosphate + AMP related_existing_claim_keys: ["mg-tpk1-thiamine-to-thdp"] curation_note: Adds explicit phosphate-transfer/AMP-product detail to the existing magnesium collection. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/sambon-2022-tpk1-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1689}] evidence_locator: Abstract evidence-scope: Recombinant enzyme [onozuka-2003-tpk1] Steady-state kinetics and mutational studies of recombinant human thiamin pyrophosphokinase (2003). https://pubmed.ncbi.nlm.nih.gov/12953792/ DOI: 10.3177/jnsv.49.156 [sambon-2022-tpk1] Product inhibition of mammalian thiamine pyrophosphokinase is an important mechanism for maintaining thiamine diphosphate homeostasis (2022). https://doi.org/10.1016/j.bbagen.2021.130071 DOI: 10.1016/j.bbagen.2021.130071
    Complete structured claim and evidence

  3. 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

  4. TPK1-deficient patients had reduced ThDP in sampled muscle and blood; blood remained low during thiamine supplementation.

    Biallelic TPK1 deficiency genotypes → Cellular thiamine diphosphate content source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence-scope
    Muscle and blood
    evidence_locator
    Table 2
    evidence_spans
    [{"source_document": "artifacts/thiamine_transport_sources/PMC3234371.txt", "start_char": 13816, "end_char": 16551}]
    experimental_model
    Five patients from three families; muscle/blood chemistry and enzyme assays.
    limitations
    Small heterogeneous series; no universal blood or tissue cutoff.
    nutrient_topic
    Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
    organism
    Homo sapiens
    plain_language
    Extra B1 intake does not guarantee normal cofactor production when activation machinery is impaired.
    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 388–400

    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-thdp TPK1-deficient patients had reduced ThDP in sampled muscle and blood; blood remained low during thiamine supplementation. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Extra B1 intake does not guarantee normal cofactor production when activation machinery is impaired. organism: Homo sapiens tissue_or_cell_type: Muscle and blood experimental_model: Five patients from three families; muscle/blood chemistry and enzyme assays. limitations: Small heterogeneous series; no universal blood or tissue cutoff. evidence_locator: Table 2 evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/PMC3234371.txt", "start_char": 13816, "end_char": 16551}] 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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