Thiamine diphosphate

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 recombinant mouse TPK1; forward and reverse reaction kinetics.

limitations

Product inhibition is a separate limit from Mg shortage.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Mus musculus

plain_language

B1 activation has product feedback even when ATP and magnesium are supplied.

primary_references

[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

Purified recombinant enzyme

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 529–539

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant mouse TPK1; forward and reverse reaction kinetics. · source_derived_draft · unverified_draft

### mg-thdp-feedback-on-tpk Accumulated ThDP inhibited the forward reaction of purified mouse TPK1. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 activation has product feedback even when ATP and magnesium are supplied. organism: Mus musculus tissue_or_cell_type: Purified recombinant enzyme experimental_model: Purified recombinant mouse TPK1; forward and reverse reaction kinetics. limitations: Product inhibition is a separate limit from Mg shortage. 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. [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

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

Human erythrocyte transketolase; sulfur-35 ThDP binding and divalent-ion reconstitution.

limitations

Binding measurement alone does not establish tissue flux.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Homo sapiens

plain_language

Tracer binding measures the vitamin-derived cofactor joining the enzyme.

primary_references

[jung-1988-tkt] Studies on the nature of thiamine pyrophosphate binding and dependency on divalent cations of transketolase from human erythrocytes (1988). https://pubmed.ncbi.nlm.nih.gov/3248678/ DOI: 10.1016/0020-711x(88)90228-5

tissue_or_cell_type

Erythrocyte enzyme

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 541–551

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human erythrocyte transketolase; sulfur-35 ThDP binding and divalent-ion reconstitution. · source_derived_draft · unverified_draft

### mg-tkt-radiolabeled-thdp-binding Sulfur-35-labeled ThDP binding was measured directly in human erythrocyte transketolase. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Tracer binding measures the vitamin-derived cofactor joining the enzyme. organism: Homo sapiens tissue_or_cell_type: Erythrocyte enzyme experimental_model: Human erythrocyte transketolase; sulfur-35 ThDP binding and divalent-ion reconstitution. limitations: Binding measurement alone does not establish tissue flux. 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. [jung-1988-tkt] Studies on the nature of thiamine pyrophosphate binding and dependency on divalent cations of transketolase from human erythrocytes (1988). https://pubmed.ncbi.nlm.nih.gov/3248678/ DOI: 10.1016/0020-711x(88)90228-5

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

Human E1b/E2b with recombinant rat BCKD kinase.

limitations

Mixed-species assay; kinase accessibility, not clinical thiamine responsiveness.

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 E1/E2; Rattus norvegicus kinase

plain_language

Cofactor occupancy also affected access to a regulatory site. The result depends on an intact loop and does not show that every genetic BCKDH defect responds to B1.

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 mixed-species assay

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 801–812

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human E1b/E2b with recombinant rat BCKD kinase. · source_derived_draft · unverified_draft

### b1-bckdh-cofactor-limits-phosphorylation ThDP reduced kinase-mediated phosphorylation of wild-type human E1b; loop-network mutations abolished this protection in the reconstituted assay. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cofactor occupancy also affected access to a regulatory site. The result depends on an intact loop and does not show that every genetic BCKDH defect responds to B1. organism: Homo sapiens E1/E2; Rattus norvegicus kinase tissue_or_cell_type: Purified mixed-species assay experimental_model: Human E1b/E2b with recombinant rat BCKD kinase. limitations: Mixed-species assay; kinase accessibility, not clinical thiamine responsiveness. 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."}] 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

cross_nutrient

ThDP occupancy enables interaction with the lipoylated E2 carrier.

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

Human apo/holo E1b crystallography and lipoyl-domain binding.

limitations

Preparation-specific structural/kinetic mechanism; not a human thiamine-dose response.

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 binding changes the enzyme shape so it can receive its lipoyl partner.

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 787–799

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human apo/holo E1b crystallography and lipoyl-domain binding. · source_derived_draft · unverified_draft

### b1-bckdh-thdp-orders-loop Apo/holo human E1b structures showed that ThDP binding orders the phosphorylation loop needed to recognize the lipoylated E2b domain. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 binding changes the enzyme shape so it can receive its lipoyl partner. organism: Homo sapiens tissue_or_cell_type: Purified proteins experimental_model: Human apo/holo E1b crystallography and lipoyl-domain binding. limitations: Preparation-specific structural/kinetic mechanism; not a human thiamine-dose response. 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: ThDP occupancy enables interaction with the lipoylated E2 carrier. 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

evidence-scope

Brain mitochondria

evidence_locator

Results: ThTP synthesis in isolated mitochondria and energy coupling

evidence_spans

[{"source_document": "artifacts/thiamine_transport_sources/gangolf-2010-thtp-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1672}]

experimental_model

Isolated rat brain mitochondria; ThDP/Pi incubation, respiratory substrates and inhibitors.

limitations

Not a demonstrated human signaling function or a TPK1 reaction.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Rattus norvegicus

plain_language

A third phosphate can be added to B1 using respiratory energy in this preparation.

primary_references

[gangolf-2010-thtp] Thiamine Triphosphate Synthesis in Rat Brain Occurs in Mitochondria and Is Coupled to the Respiratory Chain (2010). https://pmc.ncbi.nlm.nih.gov/articles/PMC2804207/ DOI: 10.1074/jbc.M109.054379

reaction

ThDP + Pi <-> ThTP + water; coupled to respiratory energy

tissue_or_cell_type

Brain mitochondria

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 602–615

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated rat brain mitochondria; ThDP/Pi incubation, respiratory substrates and inhibitors. · source_derived_draft · unverified_draft

### b1-brain-thtp-from-thdp-and-pi Rat brain mitochondria formed ThTP from ThDP and inorganic phosphate with respiratory substrates; ATP hydrolysis did not energize synthesis. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A third phosphate can be added to B1 using respiratory energy in this preparation. organism: Rattus norvegicus tissue_or_cell_type: Brain mitochondria experimental_model: Isolated rat brain mitochondria; ThDP/Pi incubation, respiratory substrates and inhibitors. limitations: Not a demonstrated human signaling function or a TPK1 reaction. reaction: ThDP + Pi <-> ThTP + water; coupled to respiratory energy evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/gangolf-2010-thtp-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1672}] evidence_locator: Results: ThTP synthesis in isolated mitochondria and energy coupling evidence-scope: Brain mitochondria [gangolf-2010-thtp] Thiamine Triphosphate Synthesis in Rat Brain Occurs in Mitochondria and Is Coupled to the Respiratory Chain (2010). https://pmc.ncbi.nlm.nih.gov/articles/PMC2804207/ DOI: 10.1074/jbc.M109.054379

evidence-scope

Colonocytes; colonic apical membranes

evidence_locator

Abstract

evidence_spans

[{"source_document": "artifacts/thiamine_transport_sources/nabokina-2012-colonic-tpp-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1813}]

experimental_model

NCM460 cells and human donor colonic apical vesicles; custom tritiated ThDP.

limitations

Does not quantify systemic contribution from gut microbial B1.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

Colon cells can absorb the phosphorylated B1 form directly.

primary_references

[nabokina-2012-colonic-tpp] A high-affinity and specific carrier-mediated mechanism for uptake of thiamine pyrophosphate by human colonic epithelial cells (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3423106/ DOI: 10.1152/ajpgi.00151.2012

tissue_or_cell_type

Colonocytes; colonic apical membranes

transport_direction

Luminal/apical compartment into colonocytes.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 502–515

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · NCM460 cells and human donor colonic apical vesicles; custom tritiated ThDP. · source_derived_draft · unverified_draft

### b1-colon-intact-thdp-uptake NCM460 colonocytes took up radiolabeled ThDP without prior substrate dephosphorylation; native human apical vesicles also showed carrier-mediated uptake. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Colon cells can absorb the phosphorylated B1 form directly. organism: Homo sapiens tissue_or_cell_type: Colonocytes; colonic apical membranes experimental_model: NCM460 cells and human donor colonic apical vesicles; custom tritiated ThDP. limitations: Does not quantify systemic contribution from gut microbial B1. transport_direction: Luminal/apical compartment into colonocytes. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/nabokina-2012-colonic-tpp-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1813}] evidence_locator: Abstract evidence-scope: Colonocytes; colonic apical membranes [nabokina-2012-colonic-tpp] A high-affinity and specific carrier-mediated mechanism for uptake of thiamine pyrophosphate by human colonic epithelial cells (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3423106/ DOI: 10.1152/ajpgi.00151.2012

evidence-scope

Purified membrane protein

evidence_locator

Results: cryo-EM structures; Supplementary Figure 1a

evidence_spans

[{"source_document": "artifacts/thiamine_transport_sources/PMC11447181.txt", "start_char": 9508, "end_char": 11196}]

experimental_model

Recombinant human SLC19A3 from Expi293F; cryo-EM and thermal-shift binding assays.

limitations

Thermal stabilization is not a direct transport-rate measurement.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

Adding phosphates changes how B1 fits this cell-surface carrier.

primary_references

[gabriel-2024-slc19a3-structure] Structural basis of thiamine transport and drug recognition by SLC19A3 (2024). https://pmc.ncbi.nlm.nih.gov/articles/PMC11447181/ DOI: 10.1038/s41467-024-52872-8

tissue_or_cell_type

Purified membrane protein

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 588–600

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human SLC19A3 from Expi293F; cryo-EM and thermal-shift binding assays. · source_derived_draft · unverified_draft

### b1-slc19a3-phosphorylation-binding-boundary Phosphorylated thiamine derivatives stabilized purified human SLC19A3 less strongly than free thiamine in binding assays. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Adding phosphates changes how B1 fits this cell-surface carrier. organism: Homo sapiens tissue_or_cell_type: Purified membrane protein experimental_model: Recombinant human SLC19A3 from Expi293F; cryo-EM and thermal-shift binding assays. limitations: Thermal stabilization is not a direct transport-rate measurement. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/PMC11447181.txt", "start_char": 9508, "end_char": 11196}] evidence_locator: Results: cryo-EM structures; Supplementary Figure 1a evidence-scope: Purified membrane protein [gabriel-2024-slc19a3-structure] Structural basis of thiamine transport and drug recognition by SLC19A3 (2024). https://pmc.ncbi.nlm.nih.gov/articles/PMC11447181/ DOI: 10.1038/s41467-024-52872-8

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

availability_state

biomarker_context Imported condition classification; unverified.

evidence_location

Abstract

evidence_span

before and after activation with exogenous thiamin diphosphate

experimental_model

Human erythrocytes incubated with thiamine, plus alcoholic, elderly and student comparison groups; HPLC ThDP versus basal and ThDP-stimulated transketolase assays.

exposure

Laboratory assessment of thiamine status using erythrocytes or whole blood

limitations

Assay response is influenced by the enzyme preparation and assay conditions; a small response is not a measurement of every tissue.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

This asks how much extra cofactor can activate the sampled enzyme, whereas HPLC counts the cofactor itself.

primary_references

[baines-1988-erythrocyte-assays] The Evaluation of Erythrocyte Thiamin Diphosphate as an Indicator of Thiamin Status in Man, and its Comparison with Erythrocyte Transketolase Activity Measurements (1988). https://journals.sagepub.com/doi/10.1177/000456328802500617 DOI: 10.1177/000456328802500617

tissue_or_cell_type

Erythrocyte hemolysates

trigger_kind

biomarker_context Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1381–1393

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human erythrocytes incubated with thiamine, plus alcoholic, elderly and student comparison groups; HPLC ThDP versus basal and ThDP-stimulated transketolase assays. · source_derived_draft · unverified_draft

### thiamine-def-exogenous-thdp-functional-assay The functional erythrocyte test compared transketolase activity before and after adding exogenous thiamine diphosphate. Condition category: biomarker_context nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This asks how much extra cofactor can activate the sampled enzyme, whereas HPLC counts the cofactor itself. organism: Homo sapiens tissue_or_cell_type: Erythrocyte hemolysates experimental_model: Human erythrocytes incubated with thiamine, plus alcoholic, elderly and student comparison groups; HPLC ThDP versus basal and ThDP-stimulated transketolase assays. limitations: Assay response is influenced by the enzyme preparation and assay conditions; a small response is not a measurement of every tissue. evidence_location: Abstract evidence_span: before and after activation with exogenous thiamin diphosphate exposure: Laboratory assessment of thiamine status using erythrocytes or whole blood [baines-1988-erythrocyte-assays] The Evaluation of Erythrocyte Thiamin Diphosphate as an Indicator of Thiamin Status in Man, and its Comparison with Erythrocyte Transketolase Activity Measurements (1988). https://journals.sagepub.com/doi/10.1177/000456328802500617 DOI: 10.1177/000456328802500617

cross_nutrient

B1-folate: phosphorylated thiamine and folates share RFC recognition; exclusive physiological counter-substrate status remains unproven.

experimental_model

Human SLC19A1 structures and HEK293F uptake assays

exposure

Binding assays and extracellular competition

limitations

Supports shared recognition; does not prove dietary B1 deficiency blocks folate delivery.

nutrient_topic

Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. · Folate (vitamin B9)

organism

Homo sapiens

plain_language

A vitamin B1 cofactor can occupy the folate carrier.

primary_references

[dang2022] Molecular mechanism of substrate recognition by folate transporter SLC19A1 (2022). https://pubmed.ncbi.nlm.nih.gov/36575193/ DOI: 10.1038/s41421-022-00508-w

tissue_or_cell_type

Purified transporter and HEK293F cells

Folate and folic acid: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 167–178

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SLC19A1 structures and HEK293F uptake assays · source_derived_draft · unverified_draft

### folate-rfc-thdp-shared-pocket Human SLC19A1 bound thiamine diphosphate in the same pocket as 5-MTHF; thiamine diphosphate inhibited methotrexate uptake with IC50 about 19 micromolar. Condition category: normal nutrient_topic: Folate and folic acid research collection; topical membership is not evidence of a direct dietary effect. plain_language: A vitamin B1 cofactor can occupy the folate carrier. organism: Homo sapiens tissue_or_cell_type: Purified transporter and HEK293F cells experimental_model: Human SLC19A1 structures and HEK293F uptake assays limitations: Supports shared recognition; does not prove dietary B1 deficiency blocks folate delivery. exposure: Binding assays and extracellular competition cross_nutrient: B1-folate: phosphorylated thiamine and folates share RFC recognition; exclusive physiological counter-substrate status remains unproven. [dang2022] Molecular mechanism of substrate recognition by folate transporter SLC19A1 (2022). https://pubmed.ncbi.nlm.nih.gov/36575193/ DOI: 10.1038/s41421-022-00508-w

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

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

Recombinant human TKT crystallography, kinetics and NMR.

limitations

Ca-supported structural preparation does not quantify native human tissue metal occupancy.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Homo sapiens

plain_language

Calcium can anchor the B1-derived cofactor in active human transketolase.

primary_references

[mitschke-2010-tkt] The Crystal Structure of Human Transketolase and New Insights into Its Mode of Action (2010). https://pmc.ncbi.nlm.nih.gov/articles/PMC2951230/ DOI: 10.1074/jbc.M110.149955

tissue_or_cell_type

Recombinant TKT crystals

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 589–599

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

### mg-tkt-calcium-thdp-anchor In recombinant human TKT, Ca2+ coordinates the ThDP diphosphate and protein ligands at the active site. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calcium can anchor the B1-derived cofactor in active human transketolase. organism: Homo sapiens tissue_or_cell_type: Recombinant TKT crystals experimental_model: Recombinant human TKT crystallography, kinetics and NMR. limitations: Ca-supported structural preparation does not quantify native human tissue metal occupancy. 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. [mitschke-2010-tkt] The Crystal Structure of Human Transketolase and New Insights into Its Mode of Action (2010). https://pmc.ncbi.nlm.nih.gov/articles/PMC2951230/ DOI: 10.1074/jbc.M110.149955

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

Recombinant human TKT crystallography, kinetics and NMR.

limitations

Retention is preparation- and protocol-specific; this is not a measurement of in vivo Mg depletion.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Homo sapiens

plain_language

The enzyme can retain loaded cofactors; free-metal changes need not immediately strip them away.

primary_references

[mitschke-2010-tkt] The Crystal Structure of Human Transketolase and New Insights into Its Mode of Action (2010). https://pmc.ncbi.nlm.nih.gov/articles/PMC2951230/ DOI: 10.1074/jbc.M110.149955

tissue_or_cell_type

Purified recombinant TKT

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 601–611

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

### mg-tkt-tight-cofactor-retention Recombinant human TKT retained ThDP and Ca2+ strongly under cofactor-removal conditions used in the study. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme can retain loaded cofactors; free-metal changes need not immediately strip them away. organism: Homo sapiens tissue_or_cell_type: Purified recombinant TKT experimental_model: Recombinant human TKT crystallography, kinetics and NMR. limitations: Retention is preparation- and protocol-specific; this is not a measurement of in vivo Mg depletion. 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. [mitschke-2010-tkt] The Crystal Structure of Human Transketolase and New Insights into Its Mode of Action (2010). https://pmc.ncbi.nlm.nih.gov/articles/PMC2951230/ DOI: 10.1074/jbc.M110.149955

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

evidence

[{"paper_key": "bezerra-2020-dhtkd1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-44"], "locator": "not included in the deposited", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]

experimental_model

1.9-A human DHTKD1 crystal structure.

limitations

Substrate-pocket interpretation is structural; an uncertain putative 2-oxoadipate density was not deposited as ligand.

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

DHTKD1 is its own B1 enzyme. Similarity to OGDH does not make the proteins interchangeable.

primary_references

[bezerra-2020-dhtkd1] Crystal structure and interaction studies of human DHTKD1 provide insight into a mitochondrial megacomplex in lysine catabolism (2020). https://pubmed.ncbi.nlm.nih.gov/32695416/ DOI: 10.1107/s205225252000696x

tissue_or_cell_type

Recombinant protein crystal

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 896–907

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 1.9-A human DHTKD1 crystal structure. · source_derived_draft · unverified_draft

### b1-dhtkd1-thdp-dimer-sites The human DHTKD1 dimer structure places ThDP-containing active sites at the subunit interface and reveals a pocket compatible with the longer 2-oxoadipate substrate. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: DHTKD1 is its own B1 enzyme. Similarity to OGDH does not make the proteins interchangeable. organism: Homo sapiens tissue_or_cell_type: Recombinant protein crystal experimental_model: 1.9-A human DHTKD1 crystal structure. limitations: Substrate-pocket interpretation is structural; an uncertain putative 2-oxoadipate density was not deposited as ligand. evidence: [{"paper_key": "bezerra-2020-dhtkd1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-44"], "locator": "not included in the deposited", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] nutrient: Thiamine (vitamin B1) [bezerra-2020-dhtkd1] Crystal structure and interaction studies of human DHTKD1 provide insight into a mitochondrial megacomplex in lysine catabolism (2020). https://pubmed.ncbi.nlm.nih.gov/32695416/ DOI: 10.1107/s205225252000696x

evidence-scope

Proteoliposomes; lymphoblasts; embryonic fibroblasts

evidence_locator

Figure 6

evidence_spans

[{"source_document": "artifacts/thiamine_transport_sources/PMC1595310.txt", "start_char": 12861, "end_char": 14293}]

experimental_model

Human recombinant carrier, patient lymphoblasts and Slc25a19-null mouse embryonic fibroblasts.

limitations

Indirect exchange assay; physiological counter-substrate stoichiometry not fixed.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Human and mouse experimental systems

plain_language

The mitochondrial carrier recognizes phosphorylated B1 differently from cell-surface thiamine carriers.

primary_references

[lindhurst-2006-slc25a19] Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia (2006). https://pmc.ncbi.nlm.nih.gov/articles/PMC1595310/ DOI: 10.1073/pnas.0607661103

tissue_or_cell_type

Proteoliposomes; lymphoblasts; embryonic fibroblasts

transport_direction

Reconstituted membrane exchange; physiological role is mitochondrial delivery.

transport_effect

depends The reconstituted assay exchanged external dATP for internal ThDP, which is the opposite of the delivery role the record attributes to it.

transport_pool

the mitochondrial matrix The reconstituted assay exchanged external dATP for internal ThDP, which is the opposite of the delivery role the record attributes to it.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 416–429

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human recombinant carrier, patient lymphoblasts and Slc25a19-null mouse embryonic fibroblasts. · source_derived_draft · unverified_draft

### b1-slc25a19-phosphorylated-substrates Human SLC25A19 proteoliposomes exchanged labeled dATP with internal ThDP or ThMP, but not free thiamine. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The mitochondrial carrier recognizes phosphorylated B1 differently from cell-surface thiamine carriers. organism: Human and mouse experimental systems tissue_or_cell_type: Proteoliposomes; lymphoblasts; embryonic fibroblasts experimental_model: Human recombinant carrier, patient lymphoblasts and Slc25a19-null mouse embryonic fibroblasts. limitations: Indirect exchange assay; physiological counter-substrate stoichiometry not fixed. evidence_locator: Figure 6 transport_direction: Reconstituted membrane exchange; physiological role is mitochondrial delivery. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/PMC1595310.txt", "start_char": 12861, "end_char": 14293}] evidence-scope: Proteoliposomes; lymphoblasts; embryonic fibroblasts [lindhurst-2006-slc25a19] Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia (2006). https://pmc.ncbi.nlm.nih.gov/articles/PMC1595310/ DOI: 10.1073/pnas.0607661103

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_location

Abstract

evidence_span

elimination half-life of 4-5 days

experimental_model

Newborn-rat cardiac cells in culture; thiamine omitted from growth medium without an added thiamine antagonist; time course and readdition experiments.

exposure

Thiamine omitted from rat cardiac-cell growth medium

limitations

A culture-specific turnover estimate, not a universal body-store half-life.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Rattus norvegicus

plain_language

The active cofactor pool gradually ran down after thiamine was removed.

primary_references

[zangen-1997-cardiac-culture] Thiamine deficiency in cardiac cells in culture (1997). https://pubmed.ncbi.nlm.nih.gov/9337073/ DOI: 10.1016/S0006-2952(97)00178-0

tissue_or_cell_type

Cultured cardiac cells

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1339–1351

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Newborn-rat cardiac cells in culture; thiamine omitted from growth medium without an added thiamine antagonist; time course and readdition experiments. · source_derived_draft · unverified_draft

### thiamine-def-cardiac-thdp-decay Intracellular thiamine diphosphate declined after thiamine withdrawal with an estimated elimination half-life of four to five days. Condition category: nutrient_deficiency nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The active cofactor pool gradually ran down after thiamine was removed. organism: Rattus norvegicus tissue_or_cell_type: Cultured cardiac cells experimental_model: Newborn-rat cardiac cells in culture; thiamine omitted from growth medium without an added thiamine antagonist; time course and readdition experiments. limitations: A culture-specific turnover estimate, not a universal body-store half-life. evidence_location: Abstract evidence_span: elimination half-life of 4-5 days exposure: Thiamine omitted from rat cardiac-cell growth medium [zangen-1997-cardiac-culture] Thiamine deficiency in cardiac cells in culture (1997). https://pubmed.ncbi.nlm.nih.gov/9337073/ DOI: 10.1016/S0006-2952(97)00178-0

cross_nutrient

Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply.

experimental_model

Human E1b crystallography, deposited structure 1DTW.

limitations

Occupancy supports cofactor architecture; clinical Mg limitation was not tested.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Homo sapiens

plain_language

The branched-chain ketoacid enzyme contains both vitamin B1-derived cofactor and magnesium.

primary_references

[aevarsson-2000-bckdh] Crystal structure of human branched-chain alpha-ketoacid dehydrogenase and the molecular basis of multienzyme complex deficiency in maple syrup urine disease (2000). https://pubmed.ncbi.nlm.nih.gov/10745006/ DOI: 10.1016/s0969-2126(00)00105-2

structure_url

https://www.ncbi.nlm.nih.gov/Structure/pdb/1DTW

tissue_or_cell_type

Recombinant E1b crystal

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 637–648

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human E1b crystallography, deposited structure 1DTW. · source_derived_draft · unverified_draft

### mg-bckdh-e1-cofactor-occupancy The human E1b coordinate model 1DTW contains two ThDP molecules and two Mg ions in its alpha2-beta2 assembly. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The branched-chain ketoacid enzyme contains both vitamin B1-derived cofactor and magnesium. organism: Homo sapiens tissue_or_cell_type: Recombinant E1b crystal experimental_model: Human E1b crystallography, deposited structure 1DTW. limitations: Occupancy supports cofactor architecture; clinical Mg limitation was not tested. cross_nutrient: Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply. structure_url: https://www.ncbi.nlm.nih.gov/Structure/pdb/1DTW [aevarsson-2000-bckdh] Crystal structure of human branched-chain alpha-ketoacid dehydrogenase and the molecular basis of multienzyme complex deficiency in maple syrup urine disease (2000). https://pubmed.ncbi.nlm.nih.gov/10745006/ DOI: 10.1016/s0969-2126(00)00105-2

cross_nutrient

Potassium and magnesium contribute distinct sites in a thiamine-dependent branched-chain ketoacid enzyme.

experimental_model

Human E1b crystallography, deposited structure 1DTW.

limitations

A structural potassium site is not a potassium-intake response experiment.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Homo sapiens

plain_language

Potassium also helps shape this B1-dependent enzyme; the metal roles are distinct.

primary_references

[aevarsson-2000-bckdh] Crystal structure of human branched-chain alpha-ketoacid dehydrogenase and the molecular basis of multienzyme complex deficiency in maple syrup urine disease (2000). https://pubmed.ncbi.nlm.nih.gov/10745006/ DOI: 10.1016/s0969-2126(00)00105-2

tissue_or_cell_type

Recombinant E1b crystal

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 650–660

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human E1b crystallography, deposited structure 1DTW. · source_derived_draft · unverified_draft

### mg-bckdh-potassium-site Human E1b contains potassium sites, including one organizing a loop near the ThDP cofactor. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Potassium also helps shape this B1-dependent enzyme; the metal roles are distinct. organism: Homo sapiens tissue_or_cell_type: Recombinant E1b crystal experimental_model: Human E1b crystallography, deposited structure 1DTW. limitations: A structural potassium site is not a potassium-intake response experiment. cross_nutrient: Potassium and magnesium contribute distinct sites in a thiamine-dependent branched-chain ketoacid enzyme. [aevarsson-2000-bckdh] Crystal structure of human branched-chain alpha-ketoacid dehydrogenase and the molecular basis of multienzyme complex deficiency in maple syrup urine disease (2000). https://pubmed.ncbi.nlm.nih.gov/10745006/ DOI: 10.1016/s0969-2126(00)00105-2

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

Recombinant mouse TPK crystal soaking with thiamine or ThDP and magnesium.

limitations

Crystal packing may affect oligomer state; nucleotide analog density was not confidently assigned.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Mus musculus

plain_language

Magnesium participates in the enzyme pocket that handles vitamin B1 phosphorylation.

primary_references

[liu-2011-tpk-structure] A new crystal form of mouse thiamin pyrophosphokinase (2011). https://pmc.ncbi.nlm.nih.gov/articles/PMC3088427/

tissue_or_cell_type

Recombinant protein crystals

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 505–515

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant mouse TPK crystal soaking with thiamine or ThDP and magnesium. · source_derived_draft · unverified_draft

### mg-mouse-tpk-metal-site Mouse TPK structures place Mg2+ adjacent to thiamine/ThDP and coordinated by active-site aspartate residues. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium participates in the enzyme pocket that handles vitamin B1 phosphorylation. organism: Mus musculus tissue_or_cell_type: Recombinant protein crystals experimental_model: Recombinant mouse TPK crystal soaking with thiamine or ThDP and magnesium. limitations: Crystal packing may affect oligomer state; nucleotide analog density was not confidently assigned. 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. [liu-2011-tpk-structure] A new crystal form of mouse thiamin pyrophosphokinase (2011). https://pmc.ncbi.nlm.nih.gov/articles/PMC3088427/

cross_nutrient

Calcium and magnesium effects on a thiamine-dependent enzyme were additive under specified assay conditions.

experimental_model

Purified pig-heart KGDHC, controlled free divalent-ion and cofactor concentrations.

limitations

Additivity depended on concentration; it does not imply Ca replaces Mg at the ThDP site.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Sus scrofa

plain_language

Calcium regulation and magnesium support can act together in the enzyme preparation.

primary_references

[panov-1996-ogdh] Independent modulation of the activity of alpha-ketoglutarate dehydrogenase complex by Ca2+ and Mg2+ (1996). https://pubmed.ncbi.nlm.nih.gov/8555212/ DOI: 10.1021/bi952101t

tissue_or_cell_type

Purified heart mitochondrial enzyme

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 687–697

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified pig-heart KGDHC, controlled free divalent-ion and cofactor concentrations. · source_derived_draft · unverified_draft

### mg-ogdh-calcium-additivity Ca and Mg stimulation of purified pig-heart KGDHC was additive over the tested lower free-ion ranges. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calcium regulation and magnesium support can act together in the enzyme preparation. organism: Sus scrofa tissue_or_cell_type: Purified heart mitochondrial enzyme experimental_model: Purified pig-heart KGDHC, controlled free divalent-ion and cofactor concentrations. limitations: Additivity depended on concentration; it does not imply Ca replaces Mg at the ThDP site. cross_nutrient: Calcium and magnesium effects on a thiamine-dependent enzyme were additive under specified assay conditions. [panov-1996-ogdh] Independent modulation of the activity of alpha-ketoglutarate dehydrogenase complex by Ca2+ and Mg2+ (1996). https://pubmed.ncbi.nlm.nih.gov/8555212/ DOI: 10.1021/bi952101t

cross_nutrient

Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply.

experimental_model

Human OGDH cryo-EM structure; deposited coordinate model 7WGR.

limitations

Structure does not establish a clinical Mg threshold or metal replacement equivalence.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Homo sapiens

plain_language

The human alpha-ketoglutarate-processing enzyme has distinct cofactor and calcium-regulatory architecture.

primary_references

[zhong-2022-ogdh] Structural basis for the activity and regulation of human α-ketoglutarate dehydrogenase revealed by Cryo-EM (2022). https://pubmed.ncbi.nlm.nih.gov/35272141/ DOI: 10.1016/j.bbrc.2022.02.093

structure_url

https://pdbj.org/mine/summary/7wgr

tissue_or_cell_type

Recombinant mitochondrial OGDH

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 662–673

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human OGDH cryo-EM structure; deposited coordinate model 7WGR. · source_derived_draft · unverified_draft

### mg-ogdh-human-cofactor-structure The human OGDH cryo-EM model 7WGR contains Mg and ThDP as well as a separate Ca-binding site. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The human alpha-ketoglutarate-processing enzyme has distinct cofactor and calcium-regulatory architecture. organism: Homo sapiens tissue_or_cell_type: Recombinant mitochondrial OGDH experimental_model: Human OGDH cryo-EM structure; deposited coordinate model 7WGR. limitations: Structure does not establish a clinical Mg threshold or metal replacement equivalence. cross_nutrient: Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply. structure_url: https://pdbj.org/mine/summary/7wgr [zhong-2022-ogdh] Structural basis for the activity and regulation of human α-ketoglutarate dehydrogenase revealed by Cryo-EM (2022). https://pubmed.ncbi.nlm.nih.gov/35272141/ DOI: 10.1016/j.bbrc.2022.02.093

cross_nutrient

Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply.

experimental_model

Purified pig-heart KGDHC, controlled free divalent-ion and cofactor concentrations.

limitations

Absence of added cofactor does not establish that all tightly bound cofactor was removed.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Sus scrofa

plain_language

Magnesium and the B1-derived cofactor jointly supported maximal enzyme activity.

primary_references

[panov-1996-ogdh] Independent modulation of the activity of alpha-ketoglutarate dehydrogenase complex by Ca2+ and Mg2+ (1996). https://pubmed.ncbi.nlm.nih.gov/8555212/ DOI: 10.1021/bi952101t

tissue_or_cell_type

Purified heart mitochondrial enzyme

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 675–685

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified pig-heart KGDHC, controlled free divalent-ion and cofactor concentrations. · source_derived_draft · unverified_draft

### mg-ogdh-stimulation-requires-thdp Mg increased purified pig-heart KGDHC activity only when ThDP was present in the assay. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Magnesium and the B1-derived cofactor jointly supported maximal enzyme activity. organism: Sus scrofa tissue_or_cell_type: Purified heart mitochondrial enzyme experimental_model: Purified pig-heart KGDHC, controlled free divalent-ion and cofactor concentrations. limitations: Absence of added cofactor does not establish that all tightly bound cofactor was removed. cross_nutrient: Magnesium and thiamine-derived ThDP intersect at mitochondrial carbon metabolism; purified-enzyme responses do not measure whole-body energy supply. [panov-1996-ogdh] Independent modulation of the activity of alpha-ketoglutarate dehydrogenase complex by Ca2+ and Mg2+ (1996). https://pubmed.ncbi.nlm.nih.gov/8555212/ DOI: 10.1021/bi952101t

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

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

Human erythrocyte apo-transketolase reconstitution kinetics.

limitations

This is a kinetic interpretation; it differs from yeast reconstitution involving rate-limiting dimerization.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Homo sapiens

plain_language

The cofactor-loading complex contains ThDP and magnesium, not ATP.

primary_references

[booth-1993-tkt] Reconstitution of holotransketolase is by a thiamin-diphosphate-magnesium complex (1993). https://pubmed.ncbi.nlm.nih.gov/8243472/ DOI: 10.1111/j.1432-1033.1993.tb18373.x

tissue_or_cell_type

Erythrocyte apoenzyme

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 577–587

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human erythrocyte apo-transketolase reconstitution kinetics. · source_derived_draft · unverified_draft

### mg-tkt-loading-lag Human erythrocyte apo-transketolase activation kinetics supported slow Mg-ThDP binding followed by slow isomerization. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cofactor-loading complex contains ThDP and magnesium, not ATP. organism: Homo sapiens tissue_or_cell_type: Erythrocyte apoenzyme experimental_model: Human erythrocyte apo-transketolase reconstitution kinetics. limitations: This is a kinetic interpretation; it differs from yeast reconstitution involving rate-limiting dimerization. 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. [booth-1993-tkt] Reconstitution of holotransketolase is by a thiamin-diphosphate-magnesium complex (1993). https://pubmed.ncbi.nlm.nih.gov/8243472/ DOI: 10.1111/j.1432-1033.1993.tb18373.x

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

Human erythrocyte transketolase; sulfur-35 ThDP binding and divalent-ion reconstitution.

limitations

Metal content in one preparation does not establish exclusive metal specificity.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Homo sapiens

plain_language

The isolated red-cell enzyme carried magnesium.

primary_references

[jung-1988-tkt] Studies on the nature of thiamine pyrophosphate binding and dependency on divalent cations of transketolase from human erythrocytes (1988). https://pubmed.ncbi.nlm.nih.gov/3248678/ DOI: 10.1016/0020-711x(88)90228-5

tissue_or_cell_type

Erythrocyte enzyme

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 553–563

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human erythrocyte transketolase; sulfur-35 ThDP binding and divalent-ion reconstitution. · source_derived_draft · unverified_draft

### mg-tkt-native-metal Native transketolase purified from human erythrocytes contained magnesium. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: The isolated red-cell enzyme carried magnesium. organism: Homo sapiens tissue_or_cell_type: Erythrocyte enzyme experimental_model: Human erythrocyte transketolase; sulfur-35 ThDP binding and divalent-ion reconstitution. limitations: Metal content in one preparation does not establish exclusive metal specificity. 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. [jung-1988-tkt] Studies on the nature of thiamine pyrophosphate binding and dependency on divalent cations of transketolase from human erythrocytes (1988). https://pubmed.ncbi.nlm.nih.gov/3248678/ DOI: 10.1016/0020-711x(88)90228-5

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

Human erythrocyte transketolase; sulfur-35 ThDP binding and divalent-ion reconstitution.

limitations

Replacement in vitro does not establish physiological substitution during Mg deficiency.

nutrient_topic

Magnesium research collection; topical membership is not evidence of a direct dietary effect. · Magnesium

organism

Homo sapiens

plain_language

Several divalent metals supported this B1-dependent enzyme; magnesium worked best here.

primary_references

[jung-1988-tkt] Studies on the nature of thiamine pyrophosphate binding and dependency on divalent cations of transketolase from human erythrocytes (1988). https://pubmed.ncbi.nlm.nih.gov/3248678/ DOI: 10.1016/0020-711x(88)90228-5

tissue_or_cell_type

Erythrocyte enzyme

Magnesium: cross-nutrient mechanisms and deficiency (2026-09-17) · lines 565–575

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human erythrocyte transketolase; sulfur-35 ThDP binding and divalent-ion reconstitution. · source_derived_draft · unverified_draft

### mg-tkt-other-divalent-cations Reconstituted erythrocyte transketolase activity ranked Co2+ < Mn2+ < Ca2+ < Mg2+ in the tested assay. Condition category: normal nutrient_topic: Magnesium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Several divalent metals supported this B1-dependent enzyme; magnesium worked best here. organism: Homo sapiens tissue_or_cell_type: Erythrocyte enzyme experimental_model: Human erythrocyte transketolase; sulfur-35 ThDP binding and divalent-ion reconstitution. limitations: Replacement in vitro does not establish physiological substitution during Mg deficiency. 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. [jung-1988-tkt] Studies on the nature of thiamine pyrophosphate binding and dependency on divalent cations of transketolase from human erythrocytes (1988). https://pubmed.ncbi.nlm.nih.gov/3248678/ DOI: 10.1016/0020-711x(88)90228-5

cross_nutrient

B1 cleavage is sequentially coupled to B5-derived CoA activation and B3-related NAD oxidation.

evidence

[{"paper_key": "foulon-2005-hacl1", "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

Intact/permeabilized rat hepatocytes and liver preparations.

limitations

Whole-pathway requirements cannot all be assigned to the isolated lyase.

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

ATP activates the fatty acid upstream, while NAD supports later oxidation. Listing all pathway cofactors does not mean HACL itself consumes ATP or NAD.

primary_references

[foulon-2005-hacl1] Breakdown of 2-hydroxylated straight chain fatty acids via peroxisomal 2-hydroxyphytanoyl-CoA lyase: a revised pathway for the alpha-oxidation of straight chain fatty acids (2005). https://pubmed.ncbi.nlm.nih.gov/15644336/ DOI: 10.1074/jbc.m413362200

tissue_or_cell_type

Liver

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1003–1015

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Intact/permeabilized rat hepatocytes and liver preparations. · source_derived_draft · unverified_draft

### b1-alpha-oxidation-activation-before-cleavage Rat liver/hepatocyte pathway experiments supported activation of 2-hydroxy-fatty acid to its CoA ester before ThDP-dependent cleavage; whole-pathway assays required ATP, CoA, Mg2+, ThDP and NAD+. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: ATP activates the fatty acid upstream, while NAD supports later oxidation. Listing all pathway cofactors does not mean HACL itself consumes ATP or NAD. organism: Rattus norvegicus tissue_or_cell_type: Liver experimental_model: Intact/permeabilized rat hepatocytes and liver preparations. limitations: Whole-pathway requirements cannot all be assigned to the isolated lyase. evidence: [{"paper_key": "foulon-2005-hacl1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1 cleavage is sequentially coupled to B5-derived CoA activation and B3-related NAD oxidation. nutrient: Thiamine (vitamin B1) [foulon-2005-hacl1] Breakdown of 2-hydroxylated straight chain fatty acids via peroxisomal 2-hydroxyphytanoyl-CoA lyase: a revised pathway for the alpha-oxidation of straight chain fatty acids (2005). https://pubmed.ncbi.nlm.nih.gov/15644336/ DOI: 10.1074/jbc.m413362200

experimental_model

Three-arm randomized trial.

exposure

Thiamine 250 mg as Pabrinex, magnesium sulfate 2 g, or both; biochemical samples at two hours. Initial magnesium-only group then received thiamine. Study regimens, not recommendations.

limitations

Most patients already had normal/high erythrocyte ThDP; an increase does not establish brain repletion. Pabrinex included other vitamins.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

The blood cofactor measurement rose after the thiamine-containing infusion.

primary_references

[b1-maguire2022] Randomised trial of intravenous thiamine and/or magnesium sulphate administration on erythrocyte transketolase activity, lactate concentrations and alcohol withdrawal scores (2022). https://pubmed.ncbi.nlm.nih.gov/35484175/ DOI: 10.1038/s41598-022-10970-x

tissue_or_cell_type

Erythrocytes

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1587–1597

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Three-arm randomized trial. · source_derived_draft · unverified_draft

### b1-aws-thiamine-raises-thdp The thiamine-containing infusion increased erythrocyte ThDP in both thiamine-treated groups at two hours. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The blood cofactor measurement rose after the thiamine-containing infusion. organism: Homo sapiens tissue_or_cell_type: Erythrocytes experimental_model: Three-arm randomized trial. limitations: Most patients already had normal/high erythrocyte ThDP; an increase does not establish brain repletion. Pabrinex included other vitamins. exposure: Thiamine 250 mg as Pabrinex, magnesium sulfate 2 g, or both; biochemical samples at two hours. Initial magnesium-only group then received thiamine. Study regimens, not recommendations. [b1-maguire2022] Randomised trial of intravenous thiamine and/or magnesium sulphate administration on erythrocyte transketolase activity, lactate concentrations and alcohol withdrawal scores (2022). https://pubmed.ncbi.nlm.nih.gov/35484175/ DOI: 10.1038/s41598-022-10970-x

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

evidence-scope

Brain mitochondria

evidence_locator

Results: ThTP synthesis in isolated mitochondria and energy coupling

evidence_spans

[{"source_document": "artifacts/thiamine_transport_sources/gangolf-2010-thtp-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1672}]

experimental_model

Isolated rat brain mitochondria; ThDP/Pi incubation, respiratory substrates and inhibitors.

limitations

Proton-motive-force dependence is supported; the proposed ATP-synthase identity was not definitively established.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Rattus norvegicus

plain_language

Intact, energized mitochondria were required for this B1-phosphate reaction.

primary_references

[gangolf-2010-thtp] Thiamine Triphosphate Synthesis in Rat Brain Occurs in Mitochondria and Is Coupled to the Respiratory Chain (2010). https://pmc.ncbi.nlm.nih.gov/articles/PMC2804207/ DOI: 10.1074/jbc.M109.054379

tissue_or_cell_type

Brain mitochondria

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 617–629

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isolated rat brain mitochondria; ThDP/Pi incubation, respiratory substrates and inhibitors. · source_derived_draft · unverified_draft

### b1-brain-thtp-proton-motive-dependence Depolarization or mitochondrial disruption inhibited ThTP synthesis in rat brain mitochondrial preparations. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Intact, energized mitochondria were required for this B1-phosphate reaction. organism: Rattus norvegicus tissue_or_cell_type: Brain mitochondria experimental_model: Isolated rat brain mitochondria; ThDP/Pi incubation, respiratory substrates and inhibitors. limitations: Proton-motive-force dependence is supported; the proposed ATP-synthase identity was not definitively established. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/gangolf-2010-thtp-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1672}] evidence_locator: Results: ThTP synthesis in isolated mitochondria and energy coupling evidence-scope: Brain mitochondria [gangolf-2010-thtp] Thiamine Triphosphate Synthesis in Rat Brain Occurs in Mitochondria and Is Coupled to the Respiratory Chain (2010). https://pmc.ncbi.nlm.nih.gov/articles/PMC2804207/ DOI: 10.1074/jbc.M109.054379

evidence

[{"paper_key": "nemeria-2018-oadh", "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

Human enzyme substrate-kinetic comparison.

limitations

The approximately 49-fold value belongs to this preparation and assay; it is not universal tissue selectivity.

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 two B1 enzymes overlap in possible substrates, but DHTKD1 is specialized for the longer amino-acid-derived ketoacid.

primary_references

[nemeria-2018-oadh] The mitochondrial 2-oxoadipate and 2-oxoglutarate dehydrogenase complexes share their E2 and E3 components for their function and both generate reactive oxygen species (2018). https://pubmed.ncbi.nlm.nih.gov/29191460/ DOI: 10.1016/j.freeradbiomed.2017.11.018

tissue_or_cell_type

Purified enzyme

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 883–894

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human enzyme substrate-kinetic comparison. · source_derived_draft · unverified_draft

### b1-dhtkd1-prefers-oxoadipate Recombinant human DHTKD1 showed approximately 49-fold greater catalytic efficiency for 2-oxoadipate than 2-oxoglutarate in the reported assay. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The two B1 enzymes overlap in possible substrates, but DHTKD1 is specialized for the longer amino-acid-derived ketoacid. organism: Homo sapiens tissue_or_cell_type: Purified enzyme experimental_model: Human enzyme substrate-kinetic comparison. limitations: The approximately 49-fold value belongs to this preparation and assay; it is not universal tissue selectivity. evidence: [{"paper_key": "nemeria-2018-oadh", "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) [nemeria-2018-oadh] The mitochondrial 2-oxoadipate and 2-oxoglutarate dehydrogenase complexes share their E2 and E3 components for their function and both generate reactive oxygen species (2018). https://pubmed.ncbi.nlm.nih.gov/29191460/ DOI: 10.1016/j.freeradbiomed.2017.11.018

cross_nutrient

B1-dependent lysine catabolism converges on the same lipoyl, CoA and NAD/FAD machinery used in OGDH.

evidence

[{"paper_key": "nemeria-2018-oadh", "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

Human recombinant component reconstitution.

limitations

Reconstituted proteins; sharing does not establish competition for limiting subunits in vivo.

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

Lysine-related carbon disposal uses a different B1-dependent E1, while sharing the downstream E2 and E3 proteins with a TCA-cycle enzyme.

primary_references

[nemeria-2018-oadh] The mitochondrial 2-oxoadipate and 2-oxoglutarate dehydrogenase complexes share their E2 and E3 components for their function and both generate reactive oxygen species (2018). https://pubmed.ncbi.nlm.nih.gov/29191460/ DOI: 10.1016/j.freeradbiomed.2017.11.018

tissue_or_cell_type

Purified complex

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 869–881

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

### b1-dhtkd1-recruits-shared-dlst-dld Human DHTKD1 supported 2-oxoadipate dehydrogenase activity when combined with the DLST and DLD components also used by OGDH. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Lysine-related carbon disposal uses a different B1-dependent E1, while sharing the downstream E2 and E3 proteins with a TCA-cycle enzyme. organism: Homo sapiens tissue_or_cell_type: Purified complex experimental_model: Human recombinant component reconstitution. limitations: Reconstituted proteins; sharing does not establish competition for limiting subunits in vivo. evidence: [{"paper_key": "nemeria-2018-oadh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract"], "locator": "Primary publication abstract", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1-dependent lysine catabolism converges on the same lipoyl, CoA and NAD/FAD machinery used in OGDH. nutrient: Thiamine (vitamin B1) [nemeria-2018-oadh] The mitochondrial 2-oxoadipate and 2-oxoglutarate dehydrogenase complexes share their E2 and E3 components for their function and both generate reactive oxygen species (2018). https://pubmed.ncbi.nlm.nih.gov/29191460/ DOI: 10.1016/j.freeradbiomed.2017.11.018

evidence

[{"paper_key": "foulon-1999-hacl1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract", "p-8"], "locator": "peroxisome targeting signal 1 variant", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]

experimental_model

Human HACL1 expression and fluorescent localization constructs.

limitations

Localization and activity used expression constructs; metal-dependence measurements in this paper were on rat enzyme.

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 cloned human protein is an active lyase with a peroxisomal address, distinct from ER-associated HACL2.

primary_references

[foulon-1999-hacl1] Purification, molecular cloning, and expression of 2-hydroxyphytanoyl-CoA lyase, a peroxisomal thiamine pyrophosphate-dependent enzyme that catalyzes the carbon-carbon bond cleavage during alpha-oxidation of 3-methyl-branched fatty acids (1999). https://pubmed.ncbi.nlm.nih.gov/10468558/ DOI: 10.1073/pnas.96.18.10039

tissue_or_cell_type

Transfected mammalian cells

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 990–1001

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human HACL1 expression and fluorescent localization constructs. · source_derived_draft · unverified_draft

### b1-hacl1-human-peroxisomal-targeting Human HACL1 expression increased lyase activity in mammalian cells, and GFP fusions showed that its C-terminal sequence could direct peroxisomal localization. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The cloned human protein is an active lyase with a peroxisomal address, distinct from ER-associated HACL2. organism: Homo sapiens tissue_or_cell_type: Transfected mammalian cells experimental_model: Human HACL1 expression and fluorescent localization constructs. limitations: Localization and activity used expression constructs; metal-dependence measurements in this paper were on rat enzyme. evidence: [{"paper_key": "foulon-1999-hacl1", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["abstract", "p-8"], "locator": "peroxisome targeting signal 1 variant", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] nutrient: Thiamine (vitamin B1) [foulon-1999-hacl1] Purification, molecular cloning, and expression of 2-hydroxyphytanoyl-CoA lyase, a peroxisomal thiamine pyrophosphate-dependent enzyme that catalyzes the carbon-carbon bond cleavage during alpha-oxidation of 3-methyl-branched fatty acids (1999). https://pubmed.ncbi.nlm.nih.gov/10468558/ DOI: 10.1073/pnas.96.18.10039

cross_nutrient

Direct B1/Mg dependence of a lipid-cleavage enzyme; not evidence that dietary Mg universally limits alpha oxidation.

evidence

[{"paper_key": "foulon-1999-hacl1", "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

Purified rat liver lyase; defined-substrate product identification.

limitations

Defined branched substrate and rat purified enzyme; not a human deficiency 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

Rattus norvegicus

plain_language

B1 and magnesium support a carbon-cleavage reaction in fatty-acid alpha oxidation. Here the measured products are a one-carbon CoA ester and a shortened aldehyde.

primary_references

[foulon-1999-hacl1] Purification, molecular cloning, and expression of 2-hydroxyphytanoyl-CoA lyase, a peroxisomal thiamine pyrophosphate-dependent enzyme that catalyzes the carbon-carbon bond cleavage during alpha-oxidation of 3-methyl-branched fatty acids (1999). https://pubmed.ncbi.nlm.nih.gov/10468558/ DOI: 10.1073/pnas.96.18.10039

tissue_or_cell_type

Liver peroxisomes

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 976–988

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified rat liver lyase; defined-substrate product identification. · source_derived_draft · unverified_draft

### b1-hacl1-rat-branched-cleavage Purified rat peroxisomal HACL1 cleaved 2-hydroxy-3-methylhexadecanoyl-CoA into formyl-CoA and 2-methylpentadecanal, with activity dependent on ThDP and Mg2+. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 and magnesium support a carbon-cleavage reaction in fatty-acid alpha oxidation. Here the measured products are a one-carbon CoA ester and a shortened aldehyde. organism: Rattus norvegicus tissue_or_cell_type: Liver peroxisomes experimental_model: Purified rat liver lyase; defined-substrate product identification. limitations: Defined branched substrate and rat purified enzyme; not a human deficiency experiment. evidence: [{"paper_key": "foulon-1999-hacl1", "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: Direct B1/Mg dependence of a lipid-cleavage enzyme; not evidence that dietary Mg universally limits alpha oxidation. nutrient: Thiamine (vitamin B1) [foulon-1999-hacl1] Purification, molecular cloning, and expression of 2-hydroxyphytanoyl-CoA lyase, a peroxisomal thiamine pyrophosphate-dependent enzyme that catalyzes the carbon-carbon bond cleavage during alpha-oxidation of 3-methyl-branched fatty acids (1999). https://pubmed.ncbi.nlm.nih.gov/10468558/ DOI: 10.1073/pnas.96.18.10039

cross_nutrient

B1-dependent cleavage uses a B5-derived CoA-ester substrate.

evidence

[{"paper_key": "kitamura-2017-hacl2", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-32"], "locator": "generated fatty aldehyde", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]

experimental_model

Human tagged HACL2 purified from HEK293T cells.

limitations

Aldehyde detected by TLC/Schiff staining; expected C17 identity is not a separate mass-spectrometric assignment. Mg omission was not this 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

B1 supports HACL2 cleavage only after the fatty acid has been activated onto CoA.

primary_references

[kitamura-2017-hacl2] Phytosphingosine degradation pathway includes fatty acid α-oxidation reactions in the endoplasmic reticulum (2017). https://pubmed.ncbi.nlm.nih.gov/28289220/ DOI: 10.1073/pnas.1700138114

tissue_or_cell_type

Purified membrane-associated protein

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1017–1029

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human tagged HACL2 purified from HEK293T cells. · source_derived_draft · unverified_draft

### b1-hacl2-thdp-dependent-coa-cleavage Affinity-purified human HACL2 produced fatty aldehyde from 2-hydroxy-C18:0-CoA, but not the free acid, and activity depended on added ThDP. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 supports HACL2 cleavage only after the fatty acid has been activated onto CoA. organism: Homo sapiens tissue_or_cell_type: Purified membrane-associated protein experimental_model: Human tagged HACL2 purified from HEK293T cells. limitations: Aldehyde detected by TLC/Schiff staining; expected C17 identity is not a separate mass-spectrometric assignment. Mg omission was not this experiment. evidence: [{"paper_key": "kitamura-2017-hacl2", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-32"], "locator": "generated fatty aldehyde", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1-dependent cleavage uses a B5-derived CoA-ester substrate. nutrient: Thiamine (vitamin B1) [kitamura-2017-hacl2] Phytosphingosine degradation pathway includes fatty acid α-oxidation reactions in the endoplasmic reticulum (2017). https://pubmed.ncbi.nlm.nih.gov/28289220/ DOI: 10.1073/pnas.1700138114

availability_state

biomarker_context Imported condition classification; unverified.

experimental_model

Same 69-person trial; six-month biomarker measurement.

exposure

200 mg oral thiamine mononitrate daily versus placebo for six months; trial exposure only.

limitations

Biochemical uptake does not establish the rate-limiting cause of cardiac dysfunction.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

A higher vitamin measurement did not guarantee better heart function.

primary_references

[b1-keith2019] Thiamin supplementation does not improve left ventricular ejection fraction in ambulatory heart failure patients: a randomized controlled trial (2019). https://pubmed.ncbi.nlm.nih.gov/31504093/ DOI: 10.1093/ajcn/nqz192

tissue_or_cell_type

Erythrocytes and urine

trigger_kind

biomarker_context Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1696–1706

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Same 69-person trial; six-month biomarker measurement. · source_derived_draft · unverified_draft

### b1-hf-biomarker-response Erythrocyte thiamine pyrophosphate and urinary thiamine increased in the 2019 chronic-HF trial despite no functional benefit. Condition category: biomarker_context nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A higher vitamin measurement did not guarantee better heart function. organism: Homo sapiens tissue_or_cell_type: Erythrocytes and urine experimental_model: Same 69-person trial; six-month biomarker measurement. limitations: Biochemical uptake does not establish the rate-limiting cause of cardiac dysfunction. exposure: 200 mg oral thiamine mononitrate daily versus placebo for six months; trial exposure only. [b1-keith2019] Thiamin supplementation does not improve left ventricular ejection fraction in ambulatory heart failure patients: a randomized controlled trial (2019). https://pubmed.ncbi.nlm.nih.gov/31504093/ DOI: 10.1093/ajcn/nqz192

experimental_model

Same trial; infants mostly breastfed.

exposure

Maternal 0, 1.2, 2.4 or 10 mg/day thiamine from weeks 2-24 postpartum; study exposures only.

limitations

No direct measurement of each tissue cofactor pool or mortality benefit.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

Improving maternal intake changed an infant blood marker.

primary_references

[b1-gallant2021] Low-dose thiamine supplementation of lactating Cambodian mothers improves human milk thiamine concentrations: a randomized controlled trial (2021). https://pubmed.ncbi.nlm.nih.gov/33829271/ DOI: 10.1093/ajcn/nqab052

tissue_or_cell_type

Infant blood

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1819–1829

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Same trial; infants mostly breastfed. · source_derived_draft · unverified_draft

### b1-maternal-intake-infant-thdp Infant whole-blood ThDP was higher in all maternal supplementation groups than placebo at 24 weeks. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Improving maternal intake changed an infant blood marker. organism: Homo sapiens tissue_or_cell_type: Infant blood experimental_model: Same trial; infants mostly breastfed. limitations: No direct measurement of each tissue cofactor pool or mortality benefit. exposure: Maternal 0, 1.2, 2.4 or 10 mg/day thiamine from weeks 2-24 postpartum; study exposures only. [b1-gallant2021] Low-dose thiamine supplementation of lactating Cambodian mothers improves human milk thiamine concentrations: a randomized controlled trial (2021). https://pubmed.ncbi.nlm.nih.gov/33829271/ DOI: 10.1093/ajcn/nqab052

experimental_model

335 mother-infant dyads; 22-week intervention.

exposure

Maternal 0, 1.2, 2.4 or 10 mg/day thiamine from weeks 2-24 postpartum; study exposures only.

limitations

Milk concentration alone is not an infant clinical outcome; model-derived optimal-dose estimate had wide uncertainty.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

Maternal B1 intake changed the infant supply route, with a flattening response across the tested active doses.

primary_references

[b1-gallant2021] Low-dose thiamine supplementation of lactating Cambodian mothers improves human milk thiamine concentrations: a randomized controlled trial (2021). https://pubmed.ncbi.nlm.nih.gov/33829271/ DOI: 10.1093/ajcn/nqab052

tissue_or_cell_type

Human milk

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1807–1817

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 335 mother-infant dyads; 22-week intervention. · source_derived_draft · unverified_draft

### b1-maternal-intake-milk All three supplementation groups had higher milk total thiamine than placebo, without significant differences between active groups. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Maternal B1 intake changed the infant supply route, with a flattening response across the tested active doses. organism: Homo sapiens tissue_or_cell_type: Human milk experimental_model: 335 mother-infant dyads; 22-week intervention. limitations: Milk concentration alone is not an infant clinical outcome; model-derived optimal-dose estimate had wide uncertainty. exposure: Maternal 0, 1.2, 2.4 or 10 mg/day thiamine from weeks 2-24 postpartum; study exposures only. [b1-gallant2021] Low-dose thiamine supplementation of lactating Cambodian mothers improves human milk thiamine concentrations: a randomized controlled trial (2021). https://pubmed.ncbi.nlm.nih.gov/33829271/ DOI: 10.1093/ajcn/nqab052

cross_nutrient

Mg dependence remains distinct from physiological net reaction direction.

evidence-scope

Recombinant enzyme

evidence_locator

Reaction definition and sections 2.2 and 3.3

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 recombinant mouse TPK1; forward and reverse reactions.

limitations

High AMP/Mg requirements do not establish meaningful reverse flux in humans.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Mus musculus

plain_language

The activation chemistry can run backward experimentally.

primary_references

[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

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 373–386

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified recombinant mouse TPK1; forward and reverse reactions. · source_derived_draft · unverified_draft

### b1-mouse-tpk1-reverse-reaction Purified mouse TPK1 formed ATP and thiamine from ThDP plus AMP under high-AMP, magnesium-containing conditions. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The activation chemistry can run backward experimentally. organism: Mus musculus tissue_or_cell_type: Recombinant enzyme experimental_model: Purified recombinant mouse TPK1; forward and reverse reactions. limitations: High AMP/Mg requirements do not establish meaningful reverse flux in humans. cross_nutrient: Mg dependence remains distinct from physiological net reaction direction. 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: Reaction definition and sections 2.2 and 3.3 evidence-scope: Recombinant enzyme [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

cross_nutrient

B1, B5-derived CoA, B2-derived FAD and niacin-related NAD act at different steps of one complex.

evidence

[{"paper_key": "nemeria-2014-ogdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-28"], "locator": "The reaction medium contained the following in 1.0 ml", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]

experimental_model

Reconstituted human multienzyme assay.

limitations

NADH assay measures overall complex turnover, not every intermediate independently.

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-dependent E1 feeds a lipoyl/CoA transfer pathway, and E3 transfers the resulting reducing equivalents to NAD.

primary_references

[nemeria-2014-ogdh] Human 2-oxoglutarate dehydrogenase complex E1 component forms a thiamin-derived radical by aerobic oxidation of the enamine intermediate (2014). https://pubmed.ncbi.nlm.nih.gov/25210035/ DOI: 10.1074/jbc.m114.591073

tissue_or_cell_type

Purified enzyme complex

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 855–867

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Reconstituted human multienzyme assay. · source_derived_draft · unverified_draft

### b1-ogdh-complex-couples-succinyl-nadh Human OGDH, lipoylated DLST and DLD assembled into an active complex coupling 2-oxoglutarate oxidation to NADH production in the CoA-containing assay. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1-dependent E1 feeds a lipoyl/CoA transfer pathway, and E3 transfers the resulting reducing equivalents to NAD. organism: Homo sapiens tissue_or_cell_type: Purified enzyme complex experimental_model: Reconstituted human multienzyme assay. limitations: NADH assay measures overall complex turnover, not every intermediate independently. evidence: [{"paper_key": "nemeria-2014-ogdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-28"], "locator": "The reaction medium contained the following in 1.0 ml", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] cross_nutrient: B1, B5-derived CoA, B2-derived FAD and niacin-related NAD act at different steps of one complex. nutrient: Thiamine (vitamin B1) [nemeria-2014-ogdh] Human 2-oxoglutarate dehydrogenase complex E1 component forms a thiamin-derived radical by aerobic oxidation of the enamine intermediate (2014). https://pubmed.ncbi.nlm.nih.gov/25210035/ DOI: 10.1074/jbc.m114.591073

evidence

[{"paper_key": "nemeria-2014-ogdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-48"], "locator": "CD titration of E1o-h", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]

experimental_model

Human OGDH circular dichroism and related spectroscopy.

limitations

Enamine assignment integrates spectroscopy and comparative experiments; fine kinetic rates were separately measured in E. coli.

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

At this TCA-cycle step, B1 holds the carbon fragment left after carbon dioxide loss. Bacterial stopped-flow numbers in the same paper are not human kinetic constants.

primary_references

[nemeria-2014-ogdh] Human 2-oxoglutarate dehydrogenase complex E1 component forms a thiamin-derived radical by aerobic oxidation of the enamine intermediate (2014). https://pubmed.ncbi.nlm.nih.gov/25210035/ DOI: 10.1074/jbc.m114.591073

tissue_or_cell_type

Purified E1

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 842–853

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human OGDH circular dichroism and related spectroscopy. · source_derived_draft · unverified_draft

### b1-ogdh-thdp-enamine-chemistry Human recombinant OGDH reacted with 2-oxoglutarate to produce spectroscopic signals supporting a ThDP-bound post-decarboxylation enamine. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: At this TCA-cycle step, B1 holds the carbon fragment left after carbon dioxide loss. Bacterial stopped-flow numbers in the same paper are not human kinetic constants. organism: Homo sapiens tissue_or_cell_type: Purified E1 experimental_model: Human OGDH circular dichroism and related spectroscopy. limitations: Enamine assignment integrates spectroscopy and comparative experiments; fine kinetic rates were separately measured in E. coli. evidence: [{"paper_key": "nemeria-2014-ogdh", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-48"], "locator": "CD titration of E1o-h", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] nutrient: Thiamine (vitamin B1) [nemeria-2014-ogdh] Human 2-oxoglutarate dehydrogenase complex E1 component forms a thiamin-derived radical by aerobic oxidation of the enamine intermediate (2014). https://pubmed.ncbi.nlm.nih.gov/25210035/ DOI: 10.1074/jbc.m114.591073

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

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

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

evidence-scope

Purified intestinal enzyme

evidence_locator

Abstract

evidence_spans

[{"source_document": "artifacts/thiamine_transport_sources/vovk-2002-phosphatase-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 828}]

experimental_model

Calf intestinal alkaline phosphatase; pH 8.5, 30 C; substrate kinetics.

limitations

Purified bovine enzyme; does not quantify human meal absorption.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Bos taurus

plain_language

An intestinal enzyme can remove B1 phosphate groups; the two forms react at different rates.

primary_references

[vovk-2002-phosphatase] [Relative reactivity of thiamine monophosphate and thiamine diphosphate upon interaction with alkaline phosphatase] (2002). https://pubmed.ncbi.nlm.nih.gov/12199107/

tissue_or_cell_type

Purified intestinal enzyme

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 106–118

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Calf intestinal alkaline phosphatase; pH 8.5, 30 C; substrate kinetics. · source_derived_draft · unverified_draft

### b1-phosphate-ester-hydrolysis Calf intestinal alkaline phosphatase hydrolyzed ThDP and ThMP; ThDP had 53-fold higher Vmax/Km under the tested conditions. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: An intestinal enzyme can remove B1 phosphate groups; the two forms react at different rates. organism: Bos taurus tissue_or_cell_type: Purified intestinal enzyme experimental_model: Calf intestinal alkaline phosphatase; pH 8.5, 30 C; substrate kinetics. limitations: Purified bovine enzyme; does not quantify human meal absorption. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/vovk-2002-phosphatase-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 828}] evidence_locator: Abstract evidence-scope: Purified intestinal enzyme [vovk-2002-phosphatase] [Relative reactivity of thiamine monophosphate and thiamine diphosphate upon interaction with alkaline phosphatase] (2002). https://pubmed.ncbi.nlm.nih.gov/12199107/

availability_state

machinery_impairment Imported condition classification; unverified.

evidence-scope

HepG2 mitochondria

evidence_locator

Abstract

evidence_spans

[{"source_document": "artifacts/thiamine_transport_sources/subramanian-2013-mitochondrial-uptake-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1750}]

experimental_model

Mouse liver mitochondria and human SLC25A19 constructs in HepG2 cells.

limitations

Lower abundance prevents assigning the entire effect to transport kinetics.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

This inherited carrier variant limits mitochondrial cofactor uptake.

primary_references

[subramanian-2013-mitochondrial-uptake] Mitochondrial Uptake of Thiamin Pyrophosphate: Physiological and Cell Biological Aspects (2013). https://pmc.ncbi.nlm.nih.gov/articles/PMC3758298/ DOI: 10.1371/journal.pone.0073503

tissue_or_cell_type

HepG2 mitochondria

trigger_kind

machinery_impairment Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 459–471

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse liver mitochondria and human SLC25A19 constructs in HepG2 cells. · source_derived_draft · unverified_draft

### b1-slc25a19-g125s-uptake G125S expression reduced mitochondrial radiolabeled-ThDP uptake and transporter protein abundance relative to wild type. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This inherited carrier variant limits mitochondrial cofactor uptake. organism: Homo sapiens tissue_or_cell_type: HepG2 mitochondria experimental_model: Mouse liver mitochondria and human SLC25A19 constructs in HepG2 cells. limitations: Lower abundance prevents assigning the entire effect to transport kinetics. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/subramanian-2013-mitochondrial-uptake-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 1750}] evidence_locator: Abstract evidence-scope: HepG2 mitochondria [subramanian-2013-mitochondrial-uptake] Mitochondrial Uptake of Thiamin Pyrophosphate: Physiological and Cell Biological Aspects (2013). https://pmc.ncbi.nlm.nih.gov/articles/PMC3758298/ DOI: 10.1371/journal.pone.0073503

availability_state

machinery_impairment Imported condition classification; unverified.

evidence-scope

Patient lymphoblasts

evidence_locator

Table 1

evidence_spans

[{"source_document": "artifacts/thiamine_transport_sources/PMC1595310.txt", "start_char": 14675, "end_char": 15382}]

experimental_model

Human recombinant carrier, patient lymphoblasts and Slc25a19-null mouse embryonic fibroblasts.

limitations

Cultured lymphoblast fractions; not a plasma threshold.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

B1 cofactor can remain outside mitochondria when its carrier fails.

primary_references

[lindhurst-2006-slc25a19] Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia (2006). https://pmc.ncbi.nlm.nih.gov/articles/PMC1595310/ DOI: 10.1073/pnas.0607661103

tissue_or_cell_type

Patient lymphoblasts

trigger_kind

machinery_impairment Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 431–443

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human recombinant carrier, patient lymphoblasts and Slc25a19-null mouse embryonic fibroblasts. · source_derived_draft · unverified_draft

### b1-slc25a19-human-pool-separation G177A patient lymphoblasts had approximately tenfold lower mitochondrial ThDP despite modestly increased cytosolic ThDP. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 cofactor can remain outside mitochondria when its carrier fails. organism: Homo sapiens tissue_or_cell_type: Patient lymphoblasts experimental_model: Human recombinant carrier, patient lymphoblasts and Slc25a19-null mouse embryonic fibroblasts. limitations: Cultured lymphoblast fractions; not a plasma threshold. evidence_locator: Table 1 evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/PMC1595310.txt", "start_char": 14675, "end_char": 15382}] evidence-scope: Patient lymphoblasts [lindhurst-2006-slc25a19] Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia (2006). https://pmc.ncbi.nlm.nih.gov/articles/PMC1595310/ DOI: 10.1073/pnas.0607661103

availability_state

machinery_impairment Imported condition classification; unverified.

evidence-scope

Embryonic fibroblasts

evidence_locator

Table 1

evidence_spans

[{"source_document": "artifacts/thiamine_transport_sources/PMC1595310.txt", "start_char": 14675, "end_char": 15382}]

experimental_model

Human recombinant carrier, patient lymphoblasts and Slc25a19-null mouse embryonic fibroblasts.

limitations

Undetectable means below this assay detection, not proven absolute zero.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Mus musculus

plain_language

Deleting the carrier separates cellular B1 supply from mitochondrial availability.

primary_references

[lindhurst-2006-slc25a19] Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia (2006). https://pmc.ncbi.nlm.nih.gov/articles/PMC1595310/ DOI: 10.1073/pnas.0607661103

tissue_or_cell_type

Embryonic fibroblasts

trigger_kind

machinery_impairment Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 445–457

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human recombinant carrier, patient lymphoblasts and Slc25a19-null mouse embryonic fibroblasts. · source_derived_draft · unverified_draft

### b1-slc25a19-mouse-mito-depletion ThDP was undetectable in knockout fibroblast mitochondrial fractions while cytosolic ThDP increased. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Deleting the carrier separates cellular B1 supply from mitochondrial availability. organism: Mus musculus tissue_or_cell_type: Embryonic fibroblasts experimental_model: Human recombinant carrier, patient lymphoblasts and Slc25a19-null mouse embryonic fibroblasts. limitations: Undetectable means below this assay detection, not proven absolute zero. evidence_locator: Table 1 evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/PMC1595310.txt", "start_char": 14675, "end_char": 15382}] evidence-scope: Embryonic fibroblasts [lindhurst-2006-slc25a19] Knockout of Slc25a19 causes mitochondrial thiamine pyrophosphate depletion, embryonic lethality, CNS malformations, and anemia (2006). https://pmc.ncbi.nlm.nih.gov/articles/PMC1595310/ DOI: 10.1073/pnas.0607661103

availability_state

machinery_impairment Imported condition classification; unverified.

evidence-scope

Neurological phenotype

evidence_locator

Abstract

evidence_spans

[{"source_document": "artifacts/thiamine_transport_sources/spiegel-2009-slc25a19-neuropathy-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 774}]

experimental_model

Four patients aged 7-20; homozygosity mapping and clinical characterization.

limitations

Normal head circumference and urinary organic acids in this family do not describe every variant.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

Mitochondrial B1 transport disease can present after normal early development.

primary_references

[spiegel-2009-slc25a19-neuropathy] SLC25A19 mutation as a cause of neuropathy and bilateral striatal necrosis (2009). https://pubmed.ncbi.nlm.nih.gov/19798730/ DOI: 10.1002/ana.21752

tissue_or_cell_type

Neurological phenotype

trigger_kind

machinery_impairment Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 488–500

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Four patients aged 7-20; homozygosity mapping and clinical characterization. · source_derived_draft · unverified_draft

### b1-slc25a19-neuropathy-genetics Four SLC25A19-affected patients had episodic paralysis/encephalopathy and progressive polyneuropathy with bilateral striatal necrosis. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Mitochondrial B1 transport disease can present after normal early development. organism: Homo sapiens tissue_or_cell_type: Neurological phenotype experimental_model: Four patients aged 7-20; homozygosity mapping and clinical characterization. limitations: Normal head circumference and urinary organic acids in this family do not describe every variant. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/spiegel-2009-slc25a19-neuropathy-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 774}] evidence_locator: Abstract evidence-scope: Neurological phenotype [spiegel-2009-slc25a19-neuropathy] SLC25A19 mutation as a cause of neuropathy and bilateral striatal necrosis (2009). https://pubmed.ncbi.nlm.nih.gov/19798730/ DOI: 10.1002/ana.21752

evidence-scope

ARPE19; MDCK; human colon

evidence_locator

Figure 8

evidence_spans

[{"source_document": "artifacts/thiamine_transport_sources/PMC3924303.txt", "start_char": 47362, "end_char": 48692}]

experimental_model

Human SLC44A4 isoforms expressed in ARPE19 cells; polarized MDCK imaging.

limitations

Canine model expressing human protein; not direct transepithelial flux.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Human constructs; human and canine host cells

plain_language

Its membrane targeting fits entry from the gut lumen.

primary_references

[nabokina-2014-slc44a4] Molecular identification and functional characterization of the human colonic thiamine pyrophosphate transporter (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC3924303/ DOI: 10.1074/jbc.M113.528257

spatial_context

Apical membrane of polarized epithelial model.

tissue_or_cell_type

ARPE19; MDCK; human colon

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 545–558

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SLC44A4 isoforms expressed in ARPE19 cells; polarized MDCK imaging. · source_derived_draft · unverified_draft

### b1-slc44a4-apical-targeting SLC44A4 isoform-1 fusion protein predominantly localized to the apical domain of polarized MDCK cells. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Its membrane targeting fits entry from the gut lumen. organism: Human constructs; human and canine host cells tissue_or_cell_type: ARPE19; MDCK; human colon experimental_model: Human SLC44A4 isoforms expressed in ARPE19 cells; polarized MDCK imaging. limitations: Canine model expressing human protein; not direct transepithelial flux. evidence_locator: Figure 8 spatial_context: Apical membrane of polarized epithelial model. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/PMC3924303.txt", "start_char": 47362, "end_char": 48692}] evidence-scope: ARPE19; MDCK; human colon [nabokina-2014-slc44a4] Molecular identification and functional characterization of the human colonic thiamine pyrophosphate transporter (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC3924303/ DOI: 10.1074/jbc.M113.528257

evidence-scope

ARPE19; MDCK; human colon

evidence_locator

Figure 1

evidence_spans

[{"source_document": "artifacts/thiamine_transport_sources/PMC3924303.txt", "start_char": 19781, "end_char": 21596}]

experimental_model

Human SLC44A4 isoforms expressed in ARPE19 cells; polarized MDCK imaging.

limitations

Heterologous uptake; host dietary contribution unmeasured.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Human constructs; human and canine host cells

plain_language

This SLC44A4 form can carry phosphorylated B1.

primary_references

[nabokina-2014-slc44a4] Molecular identification and functional characterization of the human colonic thiamine pyrophosphate transporter (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC3924303/ DOI: 10.1074/jbc.M113.528257

tissue_or_cell_type

ARPE19; MDCK; human colon

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 517–529

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SLC44A4 isoforms expressed in ARPE19 cells; polarized MDCK imaging. · source_derived_draft · unverified_draft

### b1-slc44a4-iso1-uptake Human SLC44A4 isoform 1 expression increased ThDP uptake in ARPE19 cells. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This SLC44A4 form can carry phosphorylated B1. organism: Human constructs; human and canine host cells tissue_or_cell_type: ARPE19; MDCK; human colon experimental_model: Human SLC44A4 isoforms expressed in ARPE19 cells; polarized MDCK imaging. limitations: Heterologous uptake; host dietary contribution unmeasured. evidence_locator: Figure 1 evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/PMC3924303.txt", "start_char": 19781, "end_char": 21596}] evidence-scope: ARPE19; MDCK; human colon [nabokina-2014-slc44a4] Molecular identification and functional characterization of the human colonic thiamine pyrophosphate transporter (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC3924303/ DOI: 10.1074/jbc.M113.528257

evidence-scope

ARPE19; MDCK; human colon

evidence_locator

Figure 10

evidence_spans

[{"source_document": "artifacts/thiamine_transport_sources/PMC3924303.txt", "start_char": 39610, "end_char": 40292}]

experimental_model

Human SLC44A4 isoforms expressed in ARPE19 cells; polarized MDCK imaging.

limitations

Not evidence for untested isoform 2.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Human constructs; human and canine host cells

plain_language

A second splice form retained transport activity.

primary_references

[nabokina-2014-slc44a4] Molecular identification and functional characterization of the human colonic thiamine pyrophosphate transporter (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC3924303/ DOI: 10.1074/jbc.M113.528257

tissue_or_cell_type

ARPE19; MDCK; human colon

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 531–543

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human SLC44A4 isoforms expressed in ARPE19 cells; polarized MDCK imaging. · source_derived_draft · unverified_draft

### b1-slc44a4-iso3-uptake Expressed SLC44A4 isoform 3 also supported ThDP uptake. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: A second splice form retained transport activity. organism: Human constructs; human and canine host cells tissue_or_cell_type: ARPE19; MDCK; human colon experimental_model: Human SLC44A4 isoforms expressed in ARPE19 cells; polarized MDCK imaging. limitations: Not evidence for untested isoform 2. evidence_locator: Figure 10 evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/PMC3924303.txt", "start_char": 39610, "end_char": 40292}] evidence-scope: ARPE19; MDCK; human colon [nabokina-2014-slc44a4] Molecular identification and functional characterization of the human colonic thiamine pyrophosphate transporter (2014). https://pmc.ncbi.nlm.nih.gov/articles/PMC3924303/ DOI: 10.1074/jbc.M113.528257

availability_state

machinery_impairment Imported condition classification; unverified.

evidence-scope

Colon

evidence_locator

Abstract

evidence_spans

[{"source_document": "artifacts/thiamine_transport_sources/sabui-2024-slc44a4-knockout-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 2031}]

experimental_model

Cre-Lox Slc44a4 knockout mice versus littermates; uptake and DSS challenge.

limitations

Does not quantify human systemic B1 supply.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Mus musculus

plain_language

The carrier accounts for most measured colonic uptake in this model.

primary_references

[sabui-2024-slc44a4-knockout] Effect of knocking out mouse Slc44a4 on colonic uptake of the microbiota-generated thiamine pyrophosphate and colon physiology (2024). https://pubmed.ncbi.nlm.nih.gov/38713615/ DOI: 10.1152/ajpgi.00065.2024

tissue_or_cell_type

Colon

trigger_kind

machinery_impairment Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 560–572

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cre-Lox Slc44a4 knockout mice versus littermates; uptake and DSS challenge. · source_derived_draft · unverified_draft

### b1-slc44a4-mouse-uptake-loss Slc44a4 knockout nearly eliminated carrier-mediated colonic radiolabeled-ThDP uptake in mice. Condition category: machinery_impairment nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The carrier accounts for most measured colonic uptake in this model. organism: Mus musculus tissue_or_cell_type: Colon experimental_model: Cre-Lox Slc44a4 knockout mice versus littermates; uptake and DSS challenge. limitations: Does not quantify human systemic B1 supply. evidence_spans: [{"source_document": "artifacts/thiamine_transport_sources/sabui-2024-slc44a4-knockout-source-record.json", "source_field": "resultList.result[0].abstractText", "start_char": 0, "end_char": 2031}] evidence_locator: Abstract evidence-scope: Colon [sabui-2024-slc44a4-knockout] Effect of knocking out mouse Slc44a4 on colonic uptake of the microbiota-generated thiamine pyrophosphate and colon physiology (2024). https://pubmed.ncbi.nlm.nih.gov/38713615/ DOI: 10.1152/ajpgi.00065.2024

evidence

[{"paper_key": "mitschke-2010-tkt", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-31", "p-44", "p-46", "p-47"], "locator": "acid quench", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]

experimental_model

Human recombinant TKT; chemical quench and NMR.

limitations

Acid quench protonates the intermediate; native enamine occupancy is inferred from trapped species.

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 temporarily carries the two-carbon sugar fragment before its transfer to an acceptor; the detected acid-trapped form is distinguished from the reactive enamine.

primary_references

[mitschke-2010-tkt] The crystal structure of human transketolase and new insights into its mode of action (2010). https://pubmed.ncbi.nlm.nih.gov/20667822/ DOI: 10.1074/jbc.m110.149955

tissue_or_cell_type

Purified enzyme

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 963–974

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human recombinant TKT; chemical quench and NMR. · source_derived_draft · unverified_draft

### b1-tkt-dhe-thdp-intermediate Acid-quench NMR of human TKT identified the protonated form of the DHE-ThDP intermediate generated during the donor half-reaction. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 temporarily carries the two-carbon sugar fragment before its transfer to an acceptor; the detected acid-trapped form is distinguished from the reactive enamine. organism: Homo sapiens tissue_or_cell_type: Purified enzyme experimental_model: Human recombinant TKT; chemical quench and NMR. limitations: Acid quench protonates the intermediate; native enamine occupancy is inferred from trapped species. evidence: [{"paper_key": "mitschke-2010-tkt", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-31", "p-44", "p-46", "p-47"], "locator": "acid quench", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] nutrient: Thiamine (vitamin B1) [mitschke-2010-tkt] The crystal structure of human transketolase and new insights into its mode of action (2010). https://pubmed.ncbi.nlm.nih.gov/20667822/ DOI: 10.1074/jbc.m110.149955

evidence

[{"paper_key": "mitschke-2010-tkt", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-12"], "locator": "simplified reaction scheme", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]

experimental_model

Recombinant human TKT reaction analysis.

limitations

Direct reaction chemistry; indirect recycling effects on oxidative PPP flux need separate evidence.

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 supports sugar rearrangement, connecting pentose and glycolytic intermediates. This reaction does not directly make NADPH.

primary_references

[mitschke-2010-tkt] The crystal structure of human transketolase and new insights into its mode of action (2010). https://pubmed.ncbi.nlm.nih.gov/20667822/ DOI: 10.1074/jbc.m110.149955

tissue_or_cell_type

Purified enzyme

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 950–961

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

### b1-tkt-nonoxidative-carbon-transfer Human TKT transfers two carbons from xylulose-5-phosphate to ribose-5-phosphate, yielding glyceraldehyde-3-phosphate and sedoheptulose-7-phosphate. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: B1 supports sugar rearrangement, connecting pentose and glycolytic intermediates. This reaction does not directly make NADPH. organism: Homo sapiens tissue_or_cell_type: Purified enzyme experimental_model: Recombinant human TKT reaction analysis. limitations: Direct reaction chemistry; indirect recycling effects on oxidative PPP flux need separate evidence. evidence: [{"paper_key": "mitschke-2010-tkt", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-12"], "locator": "simplified reaction scheme", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] nutrient: Thiamine (vitamin B1) [mitschke-2010-tkt] The crystal structure of human transketolase and new insights into its mode of action (2010). https://pubmed.ncbi.nlm.nih.gov/20667822/ DOI: 10.1074/jbc.m110.149955

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

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

availability_state

biomarker_context Imported condition classification; unverified.

evidence_location

Abstract

evidence_span

ETDP is more stable than ETKA in frozen erythrocytes

experimental_model

Human erythrocytes incubated with thiamine, plus alcoholic, elderly and student comparison groups; HPLC ThDP versus basal and ThDP-stimulated transketolase assays.

exposure

Laboratory assessment of thiamine status using erythrocytes or whole blood

limitations

Historical assay comparison, not a validated stability duration for every modern collection tube or analytical platform.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

Storage can affect the chemical measurement and the functional enzyme test differently.

primary_references

[baines-1988-erythrocyte-assays] The Evaluation of Erythrocyte Thiamin Diphosphate as an Indicator of Thiamin Status in Man, and its Comparison with Erythrocyte Transketolase Activity Measurements (1988). https://journals.sagepub.com/doi/10.1177/000456328802500617 DOI: 10.1177/000456328802500617

tissue_or_cell_type

Frozen erythrocyte specimens

trigger_kind

biomarker_context Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1395–1407

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human erythrocytes incubated with thiamine, plus alcoholic, elderly and student comparison groups; HPLC ThDP versus basal and ThDP-stimulated transketolase assays. · source_derived_draft · unverified_draft

### thiamine-def-frozen-erythrocyte-stability Direct erythrocyte ThDP was more stable during frozen storage than transketolase activity in the evaluated preparations. Condition category: biomarker_context nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Storage can affect the chemical measurement and the functional enzyme test differently. organism: Homo sapiens tissue_or_cell_type: Frozen erythrocyte specimens experimental_model: Human erythrocytes incubated with thiamine, plus alcoholic, elderly and student comparison groups; HPLC ThDP versus basal and ThDP-stimulated transketolase assays. limitations: Historical assay comparison, not a validated stability duration for every modern collection tube or analytical platform. evidence_location: Abstract evidence_span: ETDP is more stable than ETKA in frozen erythrocytes exposure: Laboratory assessment of thiamine status using erythrocytes or whole blood [baines-1988-erythrocyte-assays] The Evaluation of Erythrocyte Thiamin Diphosphate as an Indicator of Thiamin Status in Man, and its Comparison with Erythrocyte Transketolase Activity Measurements (1988). https://journals.sagepub.com/doi/10.1177/000456328802500617 DOI: 10.1177/000456328802500617

availability_state

biomarker_context Imported condition classification; unverified.

evidence_location

Results 3.2; Table 2

evidence_span

Spearman correlation coefficients

experimental_model

196 healthy rural Cambodian women aged 18-45; samples from a six-month thiamine-fortified fish-sauce intervention; plasma LC-MS/MS and erythrocyte HPLC assays.

exposure

Six-month thiamine-fortified fish-sauce intervention in healthy Cambodian women

limitations

Cross-sectional correlation in healthy women does not validate a plasma cutoff for Wernicke encephalopathy.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

Plasma and red-cell markers were related, but they captured different biological variation.

primary_references

[mccann-2017-plasma-erythrocyte] Comparable Performance Characteristics of Plasma Thiamine and Erythrocyte Thiamine Diphosphate in Response to Thiamine Fortification in Rural Cambodian Women (2017). https://pmc.ncbi.nlm.nih.gov/articles/PMC5537791/ DOI: 10.3390/nu9070676

tissue_or_cell_type

Plasma and erythrocytes

trigger_kind

biomarker_context Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1451–1463

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 196 healthy rural Cambodian women aged 18-45; samples from a six-month thiamine-fortified fish-sauce intervention; plasma LC-MS/MS and erythrocyte HPLC assays. · source_derived_draft · unverified_draft

### thiamine-def-plasma-erythrocyte-imperfect-correlation Baseline plasma thiamine correlated with erythrocyte ThDP at Spearman r = 0.41 in the 196 women. Condition category: biomarker_context nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Plasma and red-cell markers were related, but they captured different biological variation. organism: Homo sapiens tissue_or_cell_type: Plasma and erythrocytes experimental_model: 196 healthy rural Cambodian women aged 18-45; samples from a six-month thiamine-fortified fish-sauce intervention; plasma LC-MS/MS and erythrocyte HPLC assays. limitations: Cross-sectional correlation in healthy women does not validate a plasma cutoff for Wernicke encephalopathy. evidence_location: Results 3.2; Table 2 evidence_span: Spearman correlation coefficients exposure: Six-month thiamine-fortified fish-sauce intervention in healthy Cambodian women [mccann-2017-plasma-erythrocyte] Comparable Performance Characteristics of Plasma Thiamine and Erythrocyte Thiamine Diphosphate in Response to Thiamine Fortification in Rural Cambodian Women (2017). https://pmc.ncbi.nlm.nih.gov/articles/PMC5537791/ DOI: 10.3390/nu9070676

availability_state

biomarker_context Imported condition classification; unverified.

evidence_location

Results 3.2; Table 2

evidence_span

n = 188

experimental_model

196 healthy rural Cambodian women aged 18-45; samples from a six-month thiamine-fortified fish-sauce intervention; plasma LC-MS/MS and erythrocyte HPLC assays.

exposure

Six-month thiamine-fortified fish-sauce intervention in healthy Cambodian women

limitations

This is a different analyte from free plasma thiamine; a moderate correlation does not make the assays interchangeable.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

The phosphorylated plasma form was also related to red-cell cofactor concentration.

primary_references

[mccann-2017-plasma-erythrocyte] Comparable Performance Characteristics of Plasma Thiamine and Erythrocyte Thiamine Diphosphate in Response to Thiamine Fortification in Rural Cambodian Women (2017). https://pmc.ncbi.nlm.nih.gov/articles/PMC5537791/ DOI: 10.3390/nu9070676

tissue_or_cell_type

Plasma and erythrocytes

trigger_kind

biomarker_context Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1465–1477

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · 196 healthy rural Cambodian women aged 18-45; samples from a six-month thiamine-fortified fish-sauce intervention; plasma LC-MS/MS and erythrocyte HPLC assays. · source_derived_draft · unverified_draft

### thiamine-def-plasma-tmp-erythrocyte-correlation Baseline plasma thiamine monophosphate correlated with erythrocyte ThDP at Spearman r = 0.57 in 188 women. Condition category: biomarker_context nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: The phosphorylated plasma form was also related to red-cell cofactor concentration. organism: Homo sapiens tissue_or_cell_type: Plasma and erythrocytes experimental_model: 196 healthy rural Cambodian women aged 18-45; samples from a six-month thiamine-fortified fish-sauce intervention; plasma LC-MS/MS and erythrocyte HPLC assays. limitations: This is a different analyte from free plasma thiamine; a moderate correlation does not make the assays interchangeable. evidence_location: Results 3.2; Table 2 evidence_span: n = 188 exposure: Six-month thiamine-fortified fish-sauce intervention in healthy Cambodian women [mccann-2017-plasma-erythrocyte] Comparable Performance Characteristics of Plasma Thiamine and Erythrocyte Thiamine Diphosphate in Response to Thiamine Fortification in Rural Cambodian Women (2017). https://pmc.ncbi.nlm.nih.gov/articles/PMC5537791/ DOI: 10.3390/nu9070676

availability_state

biomarker_context Imported condition classification; unverified.

evidence_location

Abstract Results

evidence_span

correlated strongly with that in whole blood

experimental_model

Human method-comparison study: HPLC erythrocyte/whole-blood ThDP, healthy reference cohorts and 63 patients considered at risk of deficiency compared with a transketolase activation test.

exposure

Laboratory assessment of thiamine status using erythrocytes or whole blood

limitations

Correlation is not identity or a tissue-deficiency threshold; reported reference intervals were normalized to hemoglobin and are method-specific.

nutrient_topic

Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)

organism

Homo sapiens

plain_language

Whole blood and separated red cells gave closely related ThDP results under this method.

primary_references

[talwar-2000-blood-thdp] Vitamin B(1) status assessed by direct measurement of thiamin pyrophosphate in erythrocytes or whole blood by HPLC: comparison with erythrocyte transketolase activation assay (2000). https://pubmed.ncbi.nlm.nih.gov/10794754/ DOI: 10.1093/clinchem/46.5.704

tissue_or_cell_type

Whole blood and packed erythrocytes

trigger_kind

biomarker_context Imported condition classification; unverified.

Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1409–1421

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human method-comparison study: HPLC erythrocyte/whole-blood ThDP, healthy reference cohorts and 63 patients considered at risk of deficiency compared with a transketolase activation test. · source_derived_draft · unverified_draft

### thiamine-def-wholeblood-erythrocyte-thdp-correlation HPLC whole-blood and erythrocyte ThDP measurements correlated at r = 0.97 in the study. Condition category: biomarker_context nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Whole blood and separated red cells gave closely related ThDP results under this method. organism: Homo sapiens tissue_or_cell_type: Whole blood and packed erythrocytes experimental_model: Human method-comparison study: HPLC erythrocyte/whole-blood ThDP, healthy reference cohorts and 63 patients considered at risk of deficiency compared with a transketolase activation test. limitations: Correlation is not identity or a tissue-deficiency threshold; reported reference intervals were normalized to hemoglobin and are method-specific. evidence_location: Abstract Results evidence_span: correlated strongly with that in whole blood exposure: Laboratory assessment of thiamine status using erythrocytes or whole blood [talwar-2000-blood-thdp] Vitamin B(1) status assessed by direct measurement of thiamin pyrophosphate in erythrocytes or whole blood by HPLC: comparison with erythrocyte transketolase activation assay (2000). https://pubmed.ncbi.nlm.nih.gov/10794754/ DOI: 10.1093/clinchem/46.5.704

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

Connects B2-dependent DLD abundance to the canonical B1-dependent mitochondrial complexes; this study does not demonstrate failure of thiamine treatment.

evidence_spans

[{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10767280", "locator": "XML .//body//p", "paragraph_index": 58, "char_start": 0, "char_end": 905, "evidence_access": "full-text"}]

experimental_model

Human 143B cells and mouse adult fibroblasts, riboflavin-free medium and separate DPI interventions.

exposure

Riboflavin-free medium compared with matched replete medium.

limitations

No direct PDH/OGDH flux or thiamine-response experiment; selective loss must not be generalized to all flavoproteins.

nutrient_topic

Riboflavin research collection; topical membership is not evidence of a direct dietary effect. · Riboflavin (vitamin B2)

organism

Homo sapiens

plain_language

B2 withdrawal destabilized selected flavoproteins, including the shared DLD enzyme.

primary_references

[curtabbi-2024-fmn-assembly] Regulation of respiratory complex I assembly by FMN cofactor targeting (2024). https://pubmed.ncbi.nlm.nih.gov/38145589/ DOI: 10.1016/j.redox.2023.103001

tissue_or_cell_type

143B cell proteomics

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Riboflavin: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 622–634

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human 143B cells and mouse adult fibroblasts, riboflavin-free medium and separate DPI interventions. · source_derived_draft · unverified_draft

### b2-met-depletion-dld DLD protein abundance decreased in riboflavin-depleted human 143B cells, while many other mitochondrial matrix flavoproteins did not decline. Condition category: nutrient_deficiency nutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect. plain_language: B2 withdrawal destabilized selected flavoproteins, including the shared DLD enzyme. organism: Homo sapiens tissue_or_cell_type: 143B cell proteomics experimental_model: Human 143B cells and mouse adult fibroblasts, riboflavin-free medium and separate DPI interventions. limitations: No direct PDH/OGDH flux or thiamine-response experiment; selective loss must not be generalized to all flavoproteins. exposure: Riboflavin-free medium compared with matched replete medium. cross_nutrient: Connects B2-dependent DLD abundance to the canonical B1-dependent mitochondrial complexes; this study does not demonstrate failure of thiamine treatment. evidence_spans: [{"source_bundle": "artifacts/riboflavin_metabolism_sources.json", "source_key": "PMC10767280", "locator": "XML .//body//p", "paragraph_index": 58, "char_start": 0, "char_end": 905, "evidence_access": "full-text"}] [curtabbi-2024-fmn-assembly] Regulation of respiratory complex I assembly by FMN cofactor targeting (2024). https://pubmed.ncbi.nlm.nih.gov/38145589/ DOI: 10.1016/j.redox.2023.103001

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

true

experimental_model

Membrane lysates of transiently transfected or endogenously expressing cells; serum of rats fed zinc-deficient diets

exposure

Cells cultured under experimental zinc-deficient conditions; depletion method and concentrations not specified in the abstract.

limitations

Abstract-only extraction. Individual enzyme-reaction assignments, depletion concentrations/durations, quantitative effects and human clinical implications are not established here. Hydrolysis of extracellular vitamin phosphates is distinct from intracellular cofactor activation.

nutrient_topic

Zinc research collection; topical membership is not evidence of a direct dietary effect. · Zinc

organism

Cell species not specified in abstract

plain_language

Low zinc availability reduced the experimental preparations’ ability to remove phosphate groups from B vitamins.

primary_references

[zinc-enz-bvitamins2024] Rate of hydrolysis of the phosphate esters of B vitamins is reduced by zinc deficiency: In vitro and in vivo. (2024). https://pubmed.ncbi.nlm.nih.gov/39279493/ DOI: 10.1096/fj.202401207r

tissue_or_cell_type

Cultured-cell membrane lysates

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Zinc: transport, enzyme loading, deficiency and nutrient interactions (2026-09-17) · lines 833–844

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Membrane lysates of transiently transfected or endogenously expressing cells; serum of rats fed zinc-deficient diets · source_derived_draft · unverified_draft

### zinc-enz-bvitamin-cell-hydrolysis Membrane lysates from cells cultured under zinc-deficient conditions had reduced extracellular B-vitamin phosphate-ester hydrolysis activity in the study. Condition category: nutrient_deficiency nutrient_topic: Zinc research collection; topical membership is not evidence of a direct dietary effect. plain_language: Low zinc availability reduced the experimental preparations’ ability to remove phosphate groups from B vitamins. organism: Cell species not specified in abstract tissue_or_cell_type: Cultured-cell membrane lysates experimental_model: Membrane lysates of transiently transfected or endogenously expressing cells; serum of rats fed zinc-deficient diets limitations: Abstract-only extraction. Individual enzyme-reaction assignments, depletion concentrations/durations, quantitative effects and human clinical implications are not established here. Hydrolysis of extracellular vitamin phosphates is distinct from intracellular cofactor activation. exposure: Cells cultured under experimental zinc-deficient conditions; depletion method and concentrations not specified in the abstract. cross_nutrient: true [zinc-enz-bvitamins2024] Rate of hydrolysis of the phosphate esters of B vitamins is reduced by zinc deficiency: In vitro and in vivo. (2024). https://pubmed.ncbi.nlm.nih.gov/39279493/ DOI: 10.1096/fj.202401207r

experimental_model

Recombinant human DHTKD1 and DLST; structural and biochemical assays; Two human patients; fibroblast isotope tracing and genetic complementation

limitations

DHTKD1 is the E1 component, not a stand-alone enzyme performing every complex reaction.

organism

Homo sapiens

plain_language

A three-enzyme complex converts the carbon skeleton into glutaryl-CoA.

primary_references

[bezerra2020] Crystal structure and interaction studies of human DHTKD1 provide insight into a mitochondrial megacomplex in lysine catabolism (2020). https://pmc.ncbi.nlm.nih.gov/articles/PMC7340257/ DOI: 10.1107/S205225252000696X [danhauser2012] DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3516599/ DOI: 10.1016/j.ajhg.2012.10.006

tissue_or_cell_type

Mitochondrial matrix

L-Lysine: mechanism-first literature curation (2026-09-17) · lines 125–134

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human DHTKD1 and DLST; structural and biochemical assays; Two human patients; fibroblast isotope tracing and genetic complementation · source_derived_draft · unverified_draft

### oxoadipate-dehydrogenase-complex DHTKD1 with DLST and DLD supports oxidative decarboxylation of 2-oxoadipate to glutaryl-CoA, with NADH and carbon dioxide formation. Plain language: A three-enzyme complex converts the carbon skeleton into glutaryl-CoA. Condition category: normal organism: Homo sapiens tissue_or_cell_type: Mitochondrial matrix experimental_model: Recombinant human DHTKD1 and DLST; structural and biochemical assays; Two human patients; fibroblast isotope tracing and genetic complementation limitations: DHTKD1 is the E1 component, not a stand-alone enzyme performing every complex reaction. [bezerra2020] Crystal structure and interaction studies of human DHTKD1 provide insight into a mitochondrial megacomplex in lysine catabolism (2020). https://pmc.ncbi.nlm.nih.gov/articles/PMC7340257/ DOI: 10.1107/S205225252000696X [danhauser2012] DHTKD1 mutations cause 2-aminoadipic and 2-oxoadipic aciduria (2012). https://pmc.ncbi.nlm.nih.gov/articles/PMC3516599/ DOI: 10.1016/j.ajhg.2012.10.006

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

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experimental_model

Review of thiamine deficiency and oxidative metabolic pathways in ethanol neurotoxicity

exposure

Chronic alcohol use with poor nutrition

limitations

A review, labelled as such, linking the coenzyme role to the clinical syndrome. Marchiafava-Bignami disease is rare, so the clinical anchor is narrow.

nutrient_topic

Alcohol research collection; topical membership is not evidence of a direct clinical effect, and ethanol is recorded separately from the acetaldehyde it becomes. · Ethanol

organism

Human

plain_language

Without the coenzyme the pathways that burn sugar for the brain stall.

primary_references

[alcohol-p28225048] Thiamine deficiency, oxidative metabolic pathways and ethanol-induced neurotoxicity: how poor nutrition contributes to the alcoholic syndrome, as Marchiafava-Bignami disease. (2017). https://pubmed.ncbi.nlm.nih.gov/28225048/ DOI: 10.1038/ejcn.2016.267

tissue_or_cell_type

Brain

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (2026-09-21) · lines 748–759

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Review of thiamine deficiency and oxidative metabolic pathways in ethanol neurotoxicity · source_derived_draft · unverified_draft

### alcohol-thiamine-oxidative-pathways Thiamine deficiency impairs oxidative metabolic pathways and contributes to ethanol-induced neurotoxicity, with poor nutrition contributing to the alcoholic syndrome. Condition category: nutrient_deficiency nutrient_topic: Alcohol research collection; topical membership is not evidence of a direct clinical effect, and ethanol is recorded separately from the acetaldehyde it becomes. plain_language: Without the coenzyme the pathways that burn sugar for the brain stall. organism: Human tissue_or_cell_type: Brain experimental_model: Review of thiamine deficiency and oxidative metabolic pathways in ethanol neurotoxicity limitations: A review, labelled as such, linking the coenzyme role to the clinical syndrome. Marchiafava-Bignami disease is rare, so the clinical anchor is narrow. exposure: Chronic alcohol use with poor nutrition evidence_span: {"source_cache": "artifacts/alcohol-research/28225048.abstract.txt", "locator": "Indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "14985f03480c03e14fe75f00e454323cd6f5d414f3775e5ee0d4d4da7825e8c6", "start_char": 0, "end_char": 1824, "text_sha256": "14985f03480c03e14fe75f00e454323cd6f5d414f3775e5ee0d4d4da7825e8c6"} [alcohol-p28225048] Thiamine deficiency, oxidative metabolic pathways and ethanol-induced neurotoxicity: how poor nutrition contributes to the alcoholic syndrome, as Marchiafava-Bignami disease. (2017). https://pubmed.ncbi.nlm.nih.gov/28225048/ DOI: 10.1038/ejcn.2016.267