{"id":"1fe4166c-6813-52b7-8d3f-f5c78a85e3b5","stable_key":"46d15d9e-d3b5-544d-ba01-b785aa3e4f42:b1-dld-fad-nad-lipoyl-regeneration","predicate":"reoxidizes","statement":"Human DLD uses bound FAD and transiently bound NAD+ to oxidize dihydrolipoamide; NADH-bound structures place its nicotinamide ring beside FAD.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"3128c373-b350-5cd7-b5eb-0179fe0385eb","mechanism_event_label":"The shared E3 protein resets reduced lipoyl carriers using the B2-derived flavin and B3-related NAD system, allowing another round of B1-dependent turnover.","subject":{"id":"640b6164-093b-5297-a6bf-55ac8da852ae","slug":"dld","display_name":"DLD","entity_type_key":"protein"},"object":{"id":"b5c4e83d-5757-5e08-9fc9-fa2683c78b43","slug":"protein-bound-dihydrolipoamide","display_name":"Protein-bound reduced dihydrolipoyl-lysine","entity_type_key":"chemical_species"},"evidence_count":1,"mechanism_event":{"id":"3128c373-b350-5cd7-b5eb-0179fe0385eb","stable_key":"46d15d9e-d3b5-544d-ba01-b785aa3e4f42:b1-dld-fad-nad-lipoyl-regeneration-event","event_type":"biochemical_relationship","label":"The shared E3 protein resets reduced lipoyl carriers using the B2-derived flavin and B3-related NAD system, allowing another round of B1-dependent turnover.","description":"Human DLD uses bound FAD and transiently bound NAD+ to oxidize dihydrolipoamide; NADH-bound structures place its nicotinamide ring beside FAD.","status":"provisional","compartment":{"slug":"mitochondrial-matrix","display_name":"Mitochondrial matrix"},"participants":[{"entity":{"id":"e2cd7179-f218-54e8-9ce9-7a836ae35fac","slug":"fad","display_name":"FAD","entity_type_key":"small_molecule"},"role":"bound redox cofactor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"283ed24b-06a1-50aa-9281-df3bac6ce37e","slug":"nad-plus","display_name":"NAD+","entity_type_key":"small_molecule"},"role":"oxidized nucleotide acceptor","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"9fbf2e03-16a9-5ca7-965c-0bfc07ca24da","slug":"nadh","display_name":"NADH","entity_type_key":"small_molecule"},"role":"reduced nucleotide product","stoichiometry":null,"state_label":"","sequence_order":2,"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":"regenerated carrier","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"86eb1eee-a8d1-539c-8c17-0911f69b6f1b","slug":"riboflavin","display_name":"Riboflavin (vitamin B2)","entity_type_key":"small_molecule"},"role":"FAD precursor","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"08c27a3f-552e-5c92-8688-321a9b64a0d6","slug":"nicotinamide","display_name":"Nicotinamide","entity_type_key":"small_molecule"},"role":"B3 vitamer related to NAD biosynthesis","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""},{"entity":{"id":"640b6164-093b-5297-a6bf-55ac8da852ae","slug":"dld","display_name":"DLD","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":6,"notes":""},{"entity":{"id":"b5c4e83d-5757-5e08-9fc9-fa2683c78b43","slug":"protein-bound-dihydrolipoamide","display_name":"Protein-bound reduced dihydrolipoyl-lysine","entity_type_key":"chemical_species"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":7,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"B1 performs E1 carbon chemistry; B2-derived FAD and the niacin-related NAD cofactor participate in the separate shared E3 reaction.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence","value_text":"[{\"paper_key\": \"brautigam-2005-dld\", \"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.\"}]","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human DLD crystallography with NAD+ and NADH.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Cofactor chemistry does not establish dietary B2/B3 limitation or prove rescue of B1 deficiency.","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 shared E3 protein resets reduced lipoyl carriers using the B2-derived flavin and B3-related NAD system, allowing another round of B1-dependent turnover.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[brautigam-2005-dld] Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations (2005). https://pubmed.ncbi.nlm.nih.gov/15946682/ DOI: 10.1016/j.jmb.2005.05.014","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified enzyme","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"878636de-385b-5b63-8ade-a5e9397b3b74","evidence_kind":"source_excerpt","locator":"Lines 717-729","start_line":717,"end_line":729,"excerpt":"### b1-dld-fad-nad-lipoyl-regeneration\nHuman DLD uses bound FAD and transiently bound NAD+ to oxidize dihydrolipoamide; NADH-bound structures place its nicotinamide ring beside FAD.\nCondition category: normal\nnutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The shared E3 protein resets reduced lipoyl carriers using the B2-derived flavin and B3-related NAD system, allowing another round of B1-dependent turnover.\norganism: Homo sapiens\ntissue_or_cell_type: Purified enzyme\nexperimental_model: Human DLD crystallography with NAD+ and NADH.\nlimitations: Cofactor chemistry does not establish dietary B2/B3 limitation or prove rescue of B1 deficiency.\nevidence: [{\"paper_key\": \"brautigam-2005-dld\", \"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.\"}]\ncross_nutrient: B1 performs E1 carbon chemistry; B2-derived FAD and the niacin-related NAD cofactor participate in the separate shared E3 reaction.\nnutrient: Thiamine (vitamin B1)\n[brautigam-2005-dld] Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations (2005). https://pubmed.ncbi.nlm.nih.gov/15946682/ DOI: 10.1016/j.jmb.2005.05.014","model_system":"Human DLD crystallography with NAD+ and NADH.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [brautigam-2005-dld] Crystal structure of human dihydrolipoamide dehydrogenase: NAD+/NADH binding and the structural basis of disease-causing mutations (2005). https://pubmed.ncbi.nlm.nih.gov/15946682/ DOI: 10.1016/j.jmb.2005.05.014","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}