{"id":"47f64cfc-7ccf-5466-946f-6feb293ab0c3","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:itaconyl-coa-inactivates-human-mmut","predicate":"suicide-inactivates","statement":"Itaconyl-CoA inactivated purified human MMUT by forming a stable adduct with the B12-derived deoxyadenosyl moiety.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"44ddb95a-9e30-5608-b4a8-5f42a0ba6490","mechanism_event_label":"The itaconyl-CoA experiment trapped B12 radical chemistry and stopped the purified human enzyme.","subject":{"id":"753db20b-a00f-5325-ad45-9c971c56e0fd","slug":"itaconyl-coa","display_name":"Itaconyl-CoA","entity_type_key":"small_molecule"},"object":{"id":"8f690797-c976-5a5e-886e-dc49d1b17f5a","slug":"mmut","display_name":"Human methylmalonyl-CoA mutase / MMUT","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"44ddb95a-9e30-5608-b4a8-5f42a0ba6490","stable_key":"7fc92b9e-9cbf-556e-8719-6b5244625250:itaconyl-coa-inactivates-human-mmut-event","event_type":"biochemical_relationship","label":"The itaconyl-CoA experiment trapped B12 radical chemistry and stopped the purified human enzyme.","description":"Itaconyl-CoA inactivated purified human MMUT by forming a stable adduct with the B12-derived deoxyadenosyl moiety.","status":"provisional","compartment":{"slug":"mitochondrial-matrix","display_name":"Mitochondrial matrix"},"participants":[{"entity":{"id":"07657685-74aa-5d99-8625-0f6a3b521f07","slug":"adenosylcobalamin","display_name":"5'-Deoxyadenosylcobalamin","entity_type_key":"small_molecule"},"role":"radical-generating-cofactor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"fe0ad86e-a233-56c6-94ea-a188d81ce1c0","slug":"cob-ii-alamin","display_name":"Cob(II)alamin","entity_type_key":"small_molecule"},"role":"cobalt-containing-product","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"753db20b-a00f-5325-ad45-9c971c56e0fd","slug":"itaconyl-coa","display_name":"Itaconyl-CoA","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"8f690797-c976-5a5e-886e-dc49d1b17f5a","slug":"mmut","display_name":"Human methylmalonyl-CoA mutase / MMUT","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"false","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Primary abstract; indexed Results and Figure 3E","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Purified human MMUT; inhibitor-product spectroscopy and analysis","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Itaconyl-CoA exposure in the purified-enzyme assay","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Mechanism-based inhibitor is distinct from physiological methylmalonyl-CoA; no human dietary effect inferred.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"vitamin-b12","display_name":"Vitamin B12 (cobalamins)","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The itaconyl-CoA experiment trapped B12 radical chemistry and stopped the purified human enzyme.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ruetz-2019-itaconyl-radical] Itaconyl-CoA forms a stable biradical in methylmalonyl-CoA mutase and derails its activity and repair. (2019). https://pubmed.ncbi.nlm.nih.gov/31672889/ DOI: 10.1126/science.aay0934","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified protein assay","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"6042499f-2793-5e31-87fa-e1deb9340e4e","evidence_kind":"source_excerpt","locator":"Lines 1384-1396","start_line":1384,"end_line":1396,"excerpt":"### itaconyl-coa-inactivates-human-mmut\nItaconyl-CoA inactivated purified human MMUT by forming a stable adduct with the B12-derived deoxyadenosyl moiety.\nCondition category: normal\nnutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The itaconyl-CoA experiment trapped B12 radical chemistry and stopped the purified human enzyme.\norganism: Homo sapiens\ntissue_or_cell_type: Purified protein assay\nexperimental_model: Purified human MMUT; inhibitor-product spectroscopy and analysis\nlimitations: Mechanism-based inhibitor is distinct from physiological methylmalonyl-CoA; no human dietary effect inferred.\nexposure: Itaconyl-CoA exposure in the purified-enzyme assay\ncross_nutrient: false\nevidence_location: Primary abstract; indexed Results and Figure 3E\n[ruetz-2019-itaconyl-radical] Itaconyl-CoA forms a stable biradical in methylmalonyl-CoA mutase and derails its activity and repair. (2019). https://pubmed.ncbi.nlm.nih.gov/31672889/ DOI: 10.1126/science.aay0934","model_system":"Purified human MMUT; inhibitor-product spectroscopy and analysis","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [ruetz-2019-itaconyl-radical] Itaconyl-CoA forms a stable biradical in methylmalonyl-CoA mutase and derails its activity and repair. (2019). https://pubmed.ncbi.nlm.nih.gov/31672889/ DOI: 10.1126/science.aay0934","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"73145023-2982-5848-aff2-8d8875d6b9c5","stable_key":"import-7fc92b9e-9cbf-556e-8719-6b5244625250","title":"Vitamin B12: 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. 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