{"id":"29702d7f-4fa8-51bc-ac18-d3c2893072b6","stable_key":"c3df3634-4c3a-5099-a5d9-e4f6344c1084:hadh-hydroxybutyryl-coa-oxidation","predicate":"converted_to","statement":"The human HADH homodimer reversibly oxidizes (S)-3-hydroxybutyryl-CoA to acetoacetyl-CoA while reducing NAD+ to NADH.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"c93d7a6b-cd74-5990-8cb5-4529a2f52410","mechanism_event_label":"The four-carbon hydroxy intermediate is oxidized to a keto intermediate.","subject":{"id":"888ec305-791f-5233-b33d-3351058fddcc","slug":"s-3-hydroxybutyryl-coa","display_name":"(S)-3-Hydroxybutyryl-CoA","entity_type_key":"small_molecule"},"object":{"id":"080298d2-4743-5488-aa8d-48c00985fb7b","slug":"acetoacetyl-coa","display_name":"Acetoacetyl-CoA","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"c93d7a6b-cd74-5990-8cb5-4529a2f52410","stable_key":"c3df3634-4c3a-5099-a5d9-e4f6344c1084:hadh-hydroxybutyryl-coa-oxidation-event","event_type":"biochemical_relationship","label":"The four-carbon hydroxy intermediate is oxidized to a keto intermediate.","description":"The human HADH homodimer reversibly oxidizes (S)-3-hydroxybutyryl-CoA to acetoacetyl-CoA while reducing NAD+ to NADH.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"e25b17b3-9150-5a94-8acb-e08888a9e7f6","slug":"hadh-homodimer","display_name":"HADH homodimer","entity_type_key":"protein_complex"},"role":"catalyst","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"b41bfdd7-b06c-5a6f-ab0e-45885cc67303","slug":"hadh","display_name":"Short-chain L-3-hydroxyacyl-CoA dehydrogenase / HADH","entity_type_key":"protein"},"role":"catalytic_subunit","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"888ec305-791f-5233-b33d-3351058fddcc","slug":"s-3-hydroxybutyryl-coa","display_name":"(S)-3-Hydroxybutyryl-CoA","entity_type_key":"small_molecule"},"role":"substrate","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"283ed24b-06a1-50aa-9281-df3bac6ce37e","slug":"nad-plus","display_name":"NAD+","entity_type_key":"small_molecule"},"role":"oxidizing_cofactor","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"080298d2-4743-5488-aa8d-48c00985fb7b","slug":"acetoacetyl-coa","display_name":"Acetoacetyl-CoA","entity_type_key":"small_molecule"},"role":"product","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"9fbf2e03-16a9-5ca7-965c-0bfc07ca24da","slug":"nadh","display_name":"NADH","entity_type_key":"small_molecule"},"role":"product","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"experimental_model","value_text":"Purified recombinant human HADH; substrate/product-cofactor crystal complexes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"HADH is distinct from HADHA and HSD17B10. This shared reversible reaction supports the downstream route but does not quantify lysine-specific flux in people.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The four-carbon hydroxy intermediate is oxidized to a keto intermediate.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[barycki2000] Sequestration of the active site by interdomain shifting. Crystallographic and spectroscopic evidence for distinct conformations of L-3-hydroxyacyl-CoA dehydrogenase (2000). https://pubmed.ncbi.nlm.nih.gov/10840044/ DOI: 10.1074/jbc.M004669200","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Mitochondrial short-chain hydroxyacyl-CoA metabolism; recombinant protein study","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"b8073158-7b2f-5830-bf2f-71d0715be301","evidence_kind":"source_excerpt","locator":"Lines 367-375","start_line":367,"end_line":375,"excerpt":"### hadh-hydroxybutyryl-coa-oxidation\nThe human HADH homodimer reversibly oxidizes (S)-3-hydroxybutyryl-CoA to acetoacetyl-CoA while reducing NAD+ to NADH.\nPlain language: The four-carbon hydroxy intermediate is oxidized to a keto intermediate.\nCondition category: normal\norganism: Homo sapiens\ntissue_or_cell_type: Mitochondrial short-chain hydroxyacyl-CoA metabolism; recombinant protein study\nexperimental_model: Purified recombinant human HADH; substrate/product-cofactor crystal complexes\nlimitations: HADH is distinct from HADHA and HSD17B10. This shared reversible reaction supports the downstream route but does not quantify lysine-specific flux in people.\n[barycki2000] Sequestration of the active site by interdomain shifting. Crystallographic and spectroscopic evidence for distinct conformations of L-3-hydroxyacyl-CoA dehydrogenase (2000). https://pubmed.ncbi.nlm.nih.gov/10840044/ DOI: 10.1074/jbc.M004669200","model_system":"Purified recombinant human HADH; substrate/product-cofactor crystal complexes","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact quote from the accompanying curation document, not from publisher text. Original study references: [barycki2000] Sequestration of the active site by interdomain shifting. Crystallographic and spectroscopic evidence for distinct conformations of L-3-hydroxyacyl-CoA dehydrogenase (2000). https://pubmed.ncbi.nlm.nih.gov/10840044/ DOI: 10.1074/jbc.M004669200","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"7633bde7-dcc9-5086-91c6-a45eb96857f3","stable_key":"import-c3df3634-4c3a-5099-a5d9-e4f6344c1084","title":"L-Lysine: mechanism-first literature curation (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":"93998d47c21525409ba82f1c82ededf2893dff15fbe61c7deffc175b0e298e97","revision_id":"3897e31f-6624-59e1-a053-8a81b7361632","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}