{"id":"8b0f9f43-3872-59d8-8d59-9a1a07f1bf3f","stable_key":"46d15d9e-d3b5-544d-ba01-b785aa3e4f42:b1-pdh-lipoyl-acetyl-transfer","predicate":"reductively-acetylates","statement":"Recombinant human E1 transferred radiolabel from pyruvate to the lipoylated DLAT L2 domain, directly measuring reductive acetylation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"8c3faaea-1bd4-5e47-9f78-e374218d5962","mechanism_event_label":"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.","subject":{"id":"d2a2b619-f60a-5ace-9bcb-cdf2a6e194e6","slug":"pyruvate-dehydrogenase-e1","display_name":"Human pyruvate dehydrogenase E1","entity_type_key":"protein_complex"},"object":{"id":"12e22bc4-4bc8-5a45-87bc-9274656e9dab","slug":"dlat","display_name":"Dihydrolipoyl acetyltransferase / DLAT","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"8c3faaea-1bd4-5e47-9f78-e374218d5962","stable_key":"46d15d9e-d3b5-544d-ba01-b785aa3e4f42:b1-pdh-lipoyl-acetyl-transfer-event","event_type":"biochemical_relationship","label":"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.","description":"Recombinant human E1 transferred radiolabel from pyruvate to the lipoylated DLAT L2 domain, directly measuring reductive acetylation.","status":"provisional","compartment":{"slug":"mitochondrial-matrix","display_name":"Mitochondrial matrix"},"participants":[{"entity":{"id":"91e6d4f5-fba1-542d-b68a-57cc28e1e425","slug":"pyruvate","display_name":"Pyruvate","entity_type_key":"small_molecule"},"role":"carbon substrate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"187db168-8028-5ce6-9f8b-4bc61ebad1a0","slug":"thiamine-diphosphate","display_name":"Thiamine diphosphate","entity_type_key":"small_molecule"},"role":"E1 cofactor","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"fd2197c3-5a63-55f4-8bb1-bfc1e91a0e1e","slug":"protein-bound-lipoamide","display_name":"Protein-bound oxidized lipoyl-lysine","entity_type_key":"chemical_species"},"role":"electron/acyl acceptor","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"7c007c7a-fea0-5719-9cd8-8c3b3f239b37","slug":"s-acetyl-dihydrolipoyl-dlat","display_name":"S-Acetyldihydrolipoyl DLAT","entity_type_key":"protein_state"},"role":"acylated carrier state","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"d2a2b619-f60a-5ace-9bcb-cdf2a6e194e6","slug":"pyruvate-dehydrogenase-e1","display_name":"Human pyruvate dehydrogenase E1","entity_type_key":"protein_complex"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"12e22bc4-4bc8-5a45-87bc-9274656e9dab","slug":"dlat","display_name":"Dihydrolipoyl acetyltransferase / DLAT","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"Thiamine-dependent carbon chemistry requires the separate protein-bound lipoyl carrier; free lipoic-acid supplementation was not tested.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence","value_text":"[{\"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.\"}]","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human recombinant proteins; radiolabeled pyruvate assay.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Purified-system evidence; nutritional response was not tested.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient","value_text":"Thiamine (vitamin B1)","comparator":null,"unit":null,"notes":"","entity":{"slug":"thiamine","display_name":"Thiamine (vitamin B1)","entity_type_key":"small_molecule"}},{"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":"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.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[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","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified proteins","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"eb95e0e1-aa21-557a-a025-d8fc85d2ffb4","evidence_kind":"source_excerpt","locator":"Lines 676-688","start_line":676,"end_line":688,"excerpt":"### b1-pdh-lipoyl-acetyl-transfer\nRecombinant human E1 transferred radiolabel from pyruvate to the lipoylated DLAT L2 domain, directly measuring reductive acetylation.\nCondition category: normal\nnutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect.\nplain_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.\norganism: Homo sapiens\ntissue_or_cell_type: Purified proteins\nexperimental_model: Human recombinant proteins; radiolabeled pyruvate assay.\nlimitations: Purified-system evidence; nutritional response was not tested.\nevidence: [{\"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.\"}]\ncross_nutrient: Thiamine-dependent carbon chemistry requires the separate protein-bound lipoyl carrier; free lipoic-acid supplementation was not tested.\nnutrient: Thiamine (vitamin B1)\n[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","model_system":"Human recombinant proteins; radiolabeled pyruvate assay.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study 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","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}