{"id":"0fc2c6ae-6482-5f31-a462-77183a550651","stable_key":"46d15d9e-d3b5-544d-ba01-b785aa3e4f42:b1-tpk1-deficiency-pdh-assay-rescue","predicate":"restores-assay-activity-of","statement":"Patient muscle PDH activity was deficient without added ThDP but normal or near-normal under cofactor-supplemented assay conditions.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"a64e05bd-0b24-5c7f-9810-36908ce4afea","mechanism_event_label":"Supplying cofactor directly to the assay exposed an activation problem upstream of PDH.","subject":{"id":"187db168-8028-5ce6-9f8b-4bc61ebad1a0","slug":"thiamine-diphosphate","display_name":"Thiamine diphosphate","entity_type_key":"small_molecule"},"object":{"id":"bb27ec64-1ee8-534f-bc08-a9cbde015952","slug":"pyruvate-dehydrogenase-complex-activity","display_name":"Pyruvate dehydrogenase complex activity","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"a64e05bd-0b24-5c7f-9810-36908ce4afea","stable_key":"46d15d9e-d3b5-544d-ba01-b785aa3e4f42:b1-tpk1-deficiency-pdh-assay-rescue-event","event_type":"biochemical_relationship","label":"Supplying cofactor directly to the assay exposed an activation problem upstream of PDH.","description":"Patient muscle PDH activity was deficient without added ThDP but normal or near-normal under cofactor-supplemented assay conditions.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"2aa99fac-8e2a-50cb-9163-1c266796e1b6","slug":"tpk1","display_name":"Human thiamine pyrophosphokinase 1","entity_type_key":"protein"},"role":"upstream impaired enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"d2a2b619-f60a-5ace-9bcb-cdf2a6e194e6","slug":"pyruvate-dehydrogenase-e1","display_name":"Human pyruvate dehydrogenase E1","entity_type_key":"protein_complex"},"role":"cofactor-dependent component","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"187db168-8028-5ce6-9f8b-4bc61ebad1a0","slug":"thiamine-diphosphate","display_name":"Thiamine diphosphate","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"bb27ec64-1ee8-534f-bc08-a9cbde015952","slug":"pyruvate-dehydrogenase-complex-activity","display_name":"Pyruvate dehydrogenase complex activity","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence-scope","value_text":"Muscle and blood","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_locator","value_text":"Figure 3; Table 1","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_spans","value_text":"[{\"source_document\": \"artifacts/thiamine_transport_sources/PMC3234371.txt\", \"start_char\": 12774, \"end_char\": 13380}]","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Five patients from three families; muscle/blood chemistry and enzyme assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Ex vivo cofactor rescue does not establish oral ThDP delivery or clinical efficacy.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Thiamine research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"thiamine","display_name":"Thiamine (vitamin B1)","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Supplying cofactor directly to the assay exposed an activation problem upstream of PDH.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[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","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Muscle and blood","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"c2760f1d-7f52-51b5-8c0b-10e01d185f59","evidence_kind":"source_excerpt","locator":"Lines 402-414","start_line":402,"end_line":414,"excerpt":"### b1-tpk1-deficiency-pdh-assay-rescue\nPatient muscle PDH activity was deficient without added ThDP but normal or near-normal under cofactor-supplemented assay conditions.\nCondition category: machinery_impairment\nnutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Supplying cofactor directly to the assay exposed an activation problem upstream of PDH.\norganism: Homo sapiens\ntissue_or_cell_type: Muscle and blood\nexperimental_model: Five patients from three families; muscle/blood chemistry and enzyme assays.\nlimitations: Ex vivo cofactor rescue does not establish oral ThDP delivery or clinical efficacy.\nevidence_locator: Figure 3; Table 1\nevidence_spans: [{\"source_document\": \"artifacts/thiamine_transport_sources/PMC3234371.txt\", \"start_char\": 12774, \"end_char\": 13380}]\nevidence-scope: Muscle and blood\n[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","model_system":"Five patients from three families; 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Study 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","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"158d2c03-ac8c-589f-8270-c468165ae346","stable_key":"import-46d15d9e-d3b5-544d-ba01-b785aa3e4f42","title":"Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"f376512fb3310141315548015b387833e3af45146e73fb73cd02cee20e4ddb9c","revision_id":"53bc5eda-dec8-58cc-a56f-a9eb4ab036ef","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}