{"id":"43b4479f-39be-5756-a30f-18ab7f9fc2fb","stable_key":"05a3cf47-e660-5ab3-8c32-5eba9847cf0a:thc-multiple-cyps","predicate":"metabolises","statement":"CYP2C9, CYP3A and CYP2C19 metabolised THC to multiple metabolites, but the metabolism was affected by human liver fatty acid binding protein.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"e2a2184d-8e45-5d85-a09f-fd77e4f4bad0","mechanism_event_label":"Three enzymes share the job, and a fat-carrying protein changes how fast they do it.","subject":{"id":"c96f78f4-5bca-5867-9ac1-652891d40aa0","slug":"cyp2c9","display_name":"Human cytochrome P450 2C9","entity_type_key":"protein"},"object":{"id":"5a9e5b75-e6aa-5684-ad62-8a8d60148c84","slug":"tetrahydrocannabinol","display_name":"Delta-9-tetrahydrocannabinol / THC","entity_type_key":"drug"},"evidence_count":1,"mechanism_event":{"id":"e2a2184d-8e45-5d85-a09f-fd77e4f4bad0","stable_key":"05a3cf47-e660-5ab3-8c32-5eba9847cf0a:thc-multiple-cyps-event","event_type":"biochemical_relationship","label":"Three enzymes share the job, and a fat-carrying protein changes how fast they do it.","description":"CYP2C9, CYP3A and CYP2C19 metabolised THC to multiple metabolites, but the metabolism was affected by human liver fatty acid binding protein.","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":"partner_enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"cc080b54-fd5d-5cc0-930e-2cb86c116c68","slug":"cyp2c19","display_name":"Human cytochrome P450 2C19","entity_type_key":"protein"},"role":"partner_enzyme","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"49f5fc00-f383-5cd8-b9ff-881643250743","slug":"fabp1","display_name":"Human liver fatty acid binding protein / FABP1","entity_type_key":"protein"},"role":"modulating_protein","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"4f43c3ac-ea8a-5d02-b6fa-880ca224d294","slug":"thc-hydroxylation","display_name":"Hydroxylation of THC to 11-OH-THC","entity_type_key":"cellular_process"},"role":"catalysed_reaction","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"c96f78f4-5bca-5867-9ac1-652891d40aa0","slug":"cyp2c9","display_name":"Human cytochrome P450 2C9","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"5a9e5b75-e6aa-5684-ad62-8a8d60148c84","slug":"tetrahydrocannabinol","display_name":"Delta-9-tetrahydrocannabinol / THC","entity_type_key":"drug"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/thc-research/38583809.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"29593807ef463cf784578c2920ed864667e6ef46a0125ac14757a38c6b331bb1\", \"start_char\": 0, \"end_char\": 1645, \"text_sha256\": \"29593807ef463cf784578c2920ed864667e6ef46a0125ac14757a38c6b331bb1\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Recombinant enzyme metabolism of THC with and without liver fatty acid binding protein","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"THC metabolism by CYP2C9, CYP3A and CYP2C19 with FABP1","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Adds a binding protein that changes apparent metabolism, which matters because THC is extremely lipophilic. It is a recombinant system.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates.","comparator":null,"unit":null,"notes":"","entity":{"slug":"tetrahydrocannabinol","display_name":"Delta-9-tetrahydrocannabinol / THC","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Human enzymes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Three enzymes share the job, and a fat-carrying protein changes how fast they do it.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[thc-p38583809] CYP2C9, CYP3A and CYP2C19 metabolize Δ9-tetrahydrocannabinol to multiple metabolites but metabolism is affected by human liver fatty acid binding protein (FABP1). (2024). https://pubmed.ncbi.nlm.nih.gov/38583809/ DOI: 10.1016/j.bcp.2024.116191","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Recombinant system","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"68d129fd-bfc9-5987-8087-42ee1abb1681","evidence_kind":"source_excerpt","locator":"Lines 543-554","start_line":543,"end_line":554,"excerpt":"### thc-multiple-cyps\nCYP2C9, CYP3A and CYP2C19 metabolised THC to multiple metabolites, but the metabolism was affected by human liver fatty acid binding protein.\nCondition category: normal\nnutrient_topic: THC research collection; topical membership is not evidence of a direct clinical effect, and THC is recorded separately from the endocannabinoids it imitates.\nplain_language: Three enzymes share the job, and a fat-carrying protein changes how fast they do it.\norganism: Human enzymes\ntissue_or_cell_type: Recombinant system\nexperimental_model: Recombinant enzyme metabolism of THC with and without liver fatty acid binding protein\nlimitations: Adds a binding protein that changes apparent metabolism, which matters because THC is extremely lipophilic. It is a recombinant system.\nexposure: THC metabolism by CYP2C9, CYP3A and CYP2C19 with FABP1\nevidence_span: {\"source_cache\": \"artifacts/thc-research/38583809.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"29593807ef463cf784578c2920ed864667e6ef46a0125ac14757a38c6b331bb1\", \"start_char\": 0, \"end_char\": 1645, \"text_sha256\": \"29593807ef463cf784578c2920ed864667e6ef46a0125ac14757a38c6b331bb1\"}\n[thc-p38583809] CYP2C9, CYP3A and CYP2C19 metabolize Δ9-tetrahydrocannabinol to multiple metabolites but metabolism is affected by human liver fatty acid binding protein (FABP1). (2024). https://pubmed.ncbi.nlm.nih.gov/38583809/ DOI: 10.1016/j.bcp.2024.116191","model_system":"Recombinant enzyme metabolism of THC with and without liver fatty acid binding protein","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [thc-p38583809] CYP2C9, CYP3A and CYP2C19 metabolize Δ9-tetrahydrocannabinol to multiple metabolites but metabolism is affected by human liver fatty acid binding protein (FABP1). (2024). https://pubmed.ncbi.nlm.nih.gov/38583809/ DOI: 10.1016/j.bcp.2024.116191","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"b4367320-9724-507a-bead-6932fa0a78cb","stable_key":"import-05a3cf47-e660-5ab3-8c32-5eba9847cf0a","title":"THC: the cannabinoid receptors, the endocannabinoid system it occupies, what the drug does, and the dietary fat it is built from (2026-09-21)","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":"60abc81737d18b7a50b01ca487e38291774ee15d9777651aa2d3eac8670ac3b2","revision_id":"2cba3552-af89-580d-b20a-8cfb1b14f9e7","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}