{"id":"b015d551-6a17-58a3-b1d2-a0a42941b0a3","stable_key":"c9aa15a1-8ba2-5913-b2dd-372af304bf87:fast-hmgcs2","predicate":"condenses_with_acetoacetyl_coa_to","statement":"Mitochondrial HMGCS2 catalyzes condensation of acetyl-CoA and acetoacetyl-CoA to form HMG-CoA.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"79549bfd-8b37-524f-aef5-a0b89976dbc7","mechanism_event_label":"Two carbon-carrying molecules combine on the ketone-production route.","subject":{"id":"b7ed6e4c-e560-5cee-b68f-895f21862e6f","slug":"acetyl-coa","display_name":"Acetyl-CoA","entity_type_key":"small_molecule"},"object":{"id":"81e5bb47-0c11-54c9-a0ec-5c213930c173","slug":"hmg-coa","display_name":"(S)-3-Hydroxy-3-methylglutaryl-CoA","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"79549bfd-8b37-524f-aef5-a0b89976dbc7","stable_key":"c9aa15a1-8ba2-5913-b2dd-372af304bf87:fast-hmgcs2-event","event_type":"observed_relationship","label":"Two carbon-carrying molecules combine on the ketone-production route.","description":"Mitochondrial HMGCS2 catalyzes condensation of acetyl-CoA and acetoacetyl-CoA to form HMG-CoA.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"b7ed6e4c-e560-5cee-b68f-895f21862e6f","slug":"acetyl-coa","display_name":"Acetyl-CoA","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"81e5bb47-0c11-54c9-a0ec-5c213930c173","slug":"hmg-coa","display_name":"(S)-3-Hydroxy-3-methylglutaryl-CoA","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"d005a809-2f5f-5cb1-99df-9c54d1b1b41a","slug":"hmgcs2","display_name":"Human mitochondrial HMG-CoA synthase / HMGCS2","entity_type_key":"protein"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"080298d2-4743-5488-aa8d-48c00985fb7b","slug":"acetoacetyl-coa","display_name":"Acetoacetyl-CoA","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human HMGCS1/HMGCS2 structures and catalytic reaction description.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"The mitochondrial isoform is distinct from cytosolic HMGCS1 in sterol synthesis.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished.","comparator":null,"unit":null,"notes":"","entity":{"slug":"fasting","display_name":"Fasting / abstention from energy intake","entity_type_key":"cellular_process"}},{"dimension":"plain_language","value_text":"Two carbon-carrying molecules combine on the ketone-production route.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Crystal structures of human HMG-CoA synthase isoforms provide insights into inherited ketogenesis disorders and inhibitor design. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20346956/ · DOI 10.1016/j.jmb.2010.03.034","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"42080af4-b732-5df0-bd7d-ad1b7c333b07","evidence_kind":"source_excerpt","locator":"Lines 104-110","start_line":104,"end_line":110,"excerpt":"## fast-hmgcs2\nTwo carbon-carrying molecules combine on the ketone-production route.\nMitochondrial HMGCS2 catalyzes condensation of acetyl-CoA and acetoacetyl-CoA to form HMG-CoA.\nModel: Human HMGCS1/HMGCS2 structures and catalytic reaction description.\nLimitations: The mitochondrial isoform is distinct from cytosolic HMGCS1 in sterol synthesis.\nEvidence access: Primary abstract\nCrystal structures of human HMG-CoA synthase isoforms provide insights into inherited ketogenesis disorders and inhibitor design. · 2010 · https://pubmed.ncbi.nlm.nih.gov/20346956/ · DOI 10.1016/j.jmb.2010.03.034","model_system":"Human HMGCS1/HMGCS2 structures and catalytic reaction description.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access and experimental limitations specified.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"921d1eb5-2c88-52b9-9898-60b2b5bf6029","stable_key":"import-c9aa15a1-8ba2-5913-b2dd-372af304bf87","title":"Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary-abstract references and experimental limitations individually identified. 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