{"id":"8e0923e7-f54b-52d8-a4bb-30fcdd3944da","stable_key":"fcc4fa9c-4dc8-5566-b780-1a486c4d3e72:alcohol-cyp2e1-stabilisation","predicate":"increases","statement":"Ethanol induces CYP2E1 by protein stabilisation, slowing the ubiquitin-conjugation-dependent rapid degradation of the enzyme rather than raising its synthesis.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"4295b125-c474-58d3-bfe8-7d321dd7f3cd","mechanism_event_label":"Alcohol does not make more of this enzyme; it stops the cell destroying it.","subject":{"id":"e653a47d-0723-5479-9572-6ed51aa8d5b0","slug":"ethanol","display_name":"Ethanol","entity_type_key":"drug"},"object":{"id":"2eecc630-775d-57f0-8cc9-15f22de6db7d","slug":"cyp2e1-protein-stability","display_name":"CYP2E1 protein stability against ubiquitin-dependent degradation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"4295b125-c474-58d3-bfe8-7d321dd7f3cd","stable_key":"fcc4fa9c-4dc8-5566-b780-1a486c4d3e72:alcohol-cyp2e1-stabilisation-event","event_type":"biochemical_relationship","label":"Alcohol does not make more of this enzyme; it stops the cell destroying it.","description":"Ethanol induces CYP2E1 by protein stabilisation, slowing the ubiquitin-conjugation-dependent rapid degradation of the enzyme rather than raising its synthesis.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"cab0024c-2ee0-5cdd-bc3a-d3b372868085","slug":"cyp2e1","display_name":"Human cytochrome P450 2E1","entity_type_key":"protein"},"role":"stabilised_enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"9e1c8e41-cd27-5db1-860b-5cf7df1f8155","slug":"microsomal-ethanol-oxidation","display_name":"Microsomal ethanol-oxidising activity","entity_type_key":"cellular_process"},"role":"downstream_capacity","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"e653a47d-0723-5479-9572-6ed51aa8d5b0","slug":"ethanol","display_name":"Ethanol","entity_type_key":"drug"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"2eecc630-775d-57f0-8cc9-15f22de6db7d","slug":"cyp2e1-protein-stability","display_name":"CYP2E1 protein stability against ubiquitin-dependent degradation","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/alcohol-research/8530344.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"94e862c6432092ebcc448d94b25d00e1c2d9bd38197f2a7cd774202aeaebc689\", \"start_char\": 0, \"end_char\": 909, \"text_sha256\": \"94e862c6432092ebcc448d94b25d00e1c2d9bd38197f2a7cd774202aeaebc689\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Ethanol treatment with ubiquitin conjugation and degradation assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Ethanol exposure with measurement of CYP2E1 turnover","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A protein-turnover mechanism rather than a transcriptional one. It explains why the second oxidation route appears quickly without new transcription.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Alcohol research collection; topical membership is not evidence of a direct clinical effect, and ethanol is recorded separately from the acetaldehyde it becomes.","comparator":null,"unit":null,"notes":"","entity":{"slug":"ethanol","display_name":"Ethanol","entity_type_key":"drug"}},{"dimension":"organism","value_text":"Rat and cell systems","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Alcohol does not make more of this enzyme; it stops the cell destroying it.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[alcohol-p8530344] Ethanol induces CYP2E1 by protein stabilization. Role of ubiquitin conjugation in the rapid degradation of CYP2E1. (1995). https://pubmed.ncbi.nlm.nih.gov/8530344/ DOI: 10.1074/jbc.270.50.29632","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Hepatic microsomes","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"ff3d4efa-08fb-533a-8676-20a41be208d6","evidence_kind":"source_excerpt","locator":"Lines 137-148","start_line":137,"end_line":148,"excerpt":"### alcohol-cyp2e1-stabilisation\nEthanol induces CYP2E1 by protein stabilisation, slowing the ubiquitin-conjugation-dependent rapid degradation of the enzyme rather than raising its synthesis.\nCondition category: normal\nnutrient_topic: Alcohol research collection; topical membership is not evidence of a direct clinical effect, and ethanol is recorded separately from the acetaldehyde it becomes.\nplain_language: Alcohol does not make more of this enzyme; it stops the cell destroying it.\norganism: Rat and cell systems\ntissue_or_cell_type: Hepatic microsomes\nexperimental_model: Ethanol treatment with ubiquitin conjugation and degradation assays\nlimitations: A protein-turnover mechanism rather than a transcriptional one. It explains why the second oxidation route appears quickly without new transcription.\nexposure: Ethanol exposure with measurement of CYP2E1 turnover\nevidence_span: {\"source_cache\": \"artifacts/alcohol-research/8530344.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"94e862c6432092ebcc448d94b25d00e1c2d9bd38197f2a7cd774202aeaebc689\", \"start_char\": 0, \"end_char\": 909, \"text_sha256\": \"94e862c6432092ebcc448d94b25d00e1c2d9bd38197f2a7cd774202aeaebc689\"}\n[alcohol-p8530344] Ethanol induces CYP2E1 by protein stabilization. Role of ubiquitin conjugation in the rapid degradation of CYP2E1. (1995). https://pubmed.ncbi.nlm.nih.gov/8530344/ DOI: 10.1074/jbc.270.50.29632","model_system":"Ethanol treatment with ubiquitin conjugation and degradation assays","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [alcohol-p8530344] Ethanol induces CYP2E1 by protein stabilization. Role of ubiquitin conjugation in the rapid degradation of CYP2E1. (1995). https://pubmed.ncbi.nlm.nih.gov/8530344/ DOI: 10.1074/jbc.270.50.29632","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"4b310db0-1387-548c-9e3d-6d2ed634b2cd","stable_key":"import-fcc4fa9c-4dc8-5566-b780-1a486c4d3e72","title":"Alcohol: ethanol clearance, acetaldehyde, the channels it binds, organ injury and nutrient collisions (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":"cb7e8dc390e8bf302cd5e230cadff6ce9847b4aad8a3691a308964d93ba59a85","revision_id":"4b344e1e-4129-579c-a058-50262b03f9a8","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}