{"id":"fb6e2e8a-e58a-5302-a4a0-642fa06418e8","stable_key":"ea2f0904-ab2c-5d1e-a3d4-3f7ecdd70cd6:caf-cyp3a4","predicate":"contributes_to_caffeine_oxidation","statement":"Inhibitor experiments supported CYP3A4 involvement in caffeine 8-hydroxylation to trimethyluric acid.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"5057a3d0-cb57-5fb2-a375-2ec2d3d26903","mechanism_event_label":"A minor oxidative branch differs from demethylation.","subject":{"id":"54e95ff1-4ffa-5e6f-a4cb-b47e5d2a5bda","slug":"cyp3a4","display_name":"Human cytochrome P450 3A4","entity_type_key":"protein"},"object":{"id":"efbb37cd-8bea-5003-8008-7c497df35ddc","slug":"1-3-7-trimethyluric-acid","display_name":"1,3,7-Trimethyluric acid","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"5057a3d0-cb57-5fb2-a375-2ec2d3d26903","stable_key":"ea2f0904-ab2c-5d1e-a3d4-3f7ecdd70cd6:caf-cyp3a4-event","event_type":"observed_relationship","label":"A minor oxidative branch differs from demethylation.","description":"Inhibitor experiments supported CYP3A4 involvement in caffeine 8-hydroxylation to trimethyluric acid.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"54e95ff1-4ffa-5e6f-a4cb-b47e5d2a5bda","slug":"cyp3a4","display_name":"Human cytochrome P450 3A4","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"efbb37cd-8bea-5003-8008-7c497df35ddc","slug":"1-3-7-trimethyluric-acid","display_name":"1,3,7-Trimethyluric acid","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"ef028472-7c33-583d-b52e-40676004d370","slug":"caffeine","display_name":"Caffeine","entity_type_key":"small_molecule"},"role":"context_participant","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_access","value_text":"Primary abstract","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human liver microsomes with ketoconazole and bromocriptine.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Enzyme attribution was pharmacological, not a single-enzyme knockout.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Caffeine collection; salts, coffee, species and coexposure contexts retain their identities.","comparator":null,"unit":null,"notes":"","entity":{"slug":"caffeine","display_name":"Caffeine","entity_type_key":"small_molecule"}},{"dimension":"plain_language","value_text":"A minor oxidative branch differs from demethylation.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"Fluvoxamine is a potent inhibitor of the metabolism of caffeine in vitro. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9868741/ · DOI 10.1111/j.1600-0773.1998.tb01476.x","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"7440077b-25c3-5010-b081-a592cedcb2d2","evidence_kind":"source_excerpt","locator":"Lines 220-226","start_line":220,"end_line":226,"excerpt":"## caf-cyp3a4\nA minor oxidative branch differs from demethylation.\nInhibitor experiments supported CYP3A4 involvement in caffeine 8-hydroxylation to trimethyluric acid.\nModel: Human liver microsomes with ketoconazole and bromocriptine.\nLimitations: Enzyme attribution was pharmacological, not a single-enzyme knockout.\nEvidence access: Primary abstract\nFluvoxamine is a potent inhibitor of the metabolism of caffeine in vitro. · 1998 · https://pubmed.ncbi.nlm.nih.gov/9868741/ · DOI 10.1111/j.1600-0773.1998.tb01476.x","model_system":"Human liver microsomes with ketoconazole and bromocriptine.","directness":"reported_statement","verification_status":"source_derived_draft","notes":"Original curation paraphrase; evidence access stated with the claim.","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"40a654db-878c-5471-bc6c-88f4f52599c0","stable_key":"import-ea2f0904-ab2c-5d1e-a3d4-3f7ecdd70cd6","title":"Caffeine: receptors, metabolism, nutrient interactions, adaptation and discovery questions (2026-09-18)","document_type":"imported_text","citation_label":"AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text.","file_path":"","sha256":"780d73d4abd45a0284d2cc0c646dbe8432ae347362891a4b98a19a61341a7325","revision_id":"f36ffb0a-d6df-522f-b783-5e30214b9e26","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}