{"id":"3a142485-5093-514a-9d48-03f327ec2ccf","stable_key":"fcc4fa9c-4dc8-5566-b780-1a486c4d3e72:alcohol-adh-retinoic-acid","predicate":"reduces","statement":"Retinoic acid production following retinol administration was reduced 8.5-fold in Adh4-null mice and 4.8-fold in Adh1-null mice, showing overlapping roles for Adh1 and Adh4 in both ethanol and retinol metabolism.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"5efdbc63-99d1-5ac9-ba32-ce480121dd50","mechanism_event_label":"The same enzymes that clear alcohol also turn vitamin A into its signalling form.","subject":{"id":"8d7e0898-8f46-542b-8393-50e21924f236","slug":"mouse-adh4-null","display_name":"Experimental Adh4-null mouse genotype","entity_type_key":"protein_state"},"object":{"id":"50601167-a8be-5531-a340-974741138626","slug":"retinoic-acid-production","display_name":"Production of retinoic acid from retinol","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"5efdbc63-99d1-5ac9-ba32-ce480121dd50","stable_key":"fcc4fa9c-4dc8-5566-b780-1a486c4d3e72:alcohol-adh-retinoic-acid-event","event_type":"biochemical_relationship","label":"The same enzymes that clear alcohol also turn vitamin A into its signalling form.","description":"Retinoic acid production following retinol administration was reduced 8.5-fold in Adh4-null mice and 4.8-fold in Adh1-null mice, showing overlapping roles for Adh1 and Adh4 in both ethanol and retinol metabolism.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"148c57d8-c658-5769-89e8-1194cef2a782","slug":"retinol","display_name":"All-trans-retinol","entity_type_key":"small_molecule"},"role":"substrate","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"567aa149-980c-5cf0-b3e6-5fc897d5bea7","slug":"retinoic-acid","display_name":"All-trans retinoic acid","entity_type_key":"small_molecule"},"role":"product","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"ce392c9e-6483-5914-b18b-d6a2520dbbf6","slug":"vitamin-a","display_name":"Vitamin A","entity_type_key":"chemical_species"},"role":"nutrient_source","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"836e16fc-21b3-5044-89be-63d7a3b30628","slug":"mouse-adh1-null","display_name":"Experimental Adh1-null mouse genotype","entity_type_key":"protein_state"},"role":"partial_contributor","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"8d7e0898-8f46-542b-8393-50e21924f236","slug":"mouse-adh4-null","display_name":"Experimental Adh4-null mouse genotype","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"50601167-a8be-5531-a340-974741138626","slug":"retinoic-acid-production","display_name":"Production of retinoic acid from retinol","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/alcohol-research/10358022.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"c1e4e6f0703d814d36609e71a38be53f7c36bebcfdcd3a60c52ea49625369305\", \"start_char\": 0, \"end_char\": 1272, \"text_sha256\": \"c1e4e6f0703d814d36609e71a38be53f7c36bebcfdcd3a60c52ea49625369305\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Adh1, Adh3 and Adh4 null mutant mice with ethanol, formaldehyde and retinol challenges","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Intoxicating ethanol dose, formaldehyde LD50, and retinol administration","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"A clean three-gene dissection showing which enzyme does which job. It is a mouse gene family that does not map one-to-one onto the human one.","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":"Mouse","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The same enzymes that clear alcohol also turn vitamin A into its signalling form.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[alcohol-p10358022] Metabolic deficiencies in alcohol dehydrogenase Adh1, Adh3, and Adh4 null mutant mice. Overlapping roles of Adh1 and Adh4 in ethanol clearance and metabolism of retinol to retinoic acid. (1999). https://pubmed.ncbi.nlm.nih.gov/10358022/ DOI: 10.1074/jbc.274.24.16796","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Liver and embryo","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"6f338bf4-0a14-5d8e-9bea-837c0476e30c","evidence_kind":"source_excerpt","locator":"Lines 241-252","start_line":241,"end_line":252,"excerpt":"### alcohol-adh-retinoic-acid\nRetinoic acid production following retinol administration was reduced 8.5-fold in Adh4-null mice and 4.8-fold in Adh1-null mice, showing overlapping roles for Adh1 and Adh4 in both ethanol and retinol metabolism.\nCondition category: machinery_impairment\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: The same enzymes that clear alcohol also turn vitamin A into its signalling form.\norganism: Mouse\ntissue_or_cell_type: Liver and embryo\nexperimental_model: Adh1, Adh3 and Adh4 null mutant mice with ethanol, formaldehyde and retinol challenges\nlimitations: A clean three-gene dissection showing which enzyme does which job. It is a mouse gene family that does not map one-to-one onto the human one.\nexposure: Intoxicating ethanol dose, formaldehyde LD50, and retinol administration\nevidence_span: {\"source_cache\": \"artifacts/alcohol-research/10358022.abstract.txt\", \"locator\": \"Indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"c1e4e6f0703d814d36609e71a38be53f7c36bebcfdcd3a60c52ea49625369305\", \"start_char\": 0, \"end_char\": 1272, \"text_sha256\": \"c1e4e6f0703d814d36609e71a38be53f7c36bebcfdcd3a60c52ea49625369305\"}\n[alcohol-p10358022] Metabolic deficiencies in alcohol dehydrogenase Adh1, Adh3, and Adh4 null mutant mice. Overlapping roles of Adh1 and Adh4 in ethanol clearance and metabolism of retinol to retinoic acid. (1999). https://pubmed.ncbi.nlm.nih.gov/10358022/ DOI: 10.1074/jbc.274.24.16796","model_system":"Adh1, Adh3 and Adh4 null mutant mice with ethanol, formaldehyde and retinol challenges","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [alcohol-p10358022] Metabolic deficiencies in alcohol dehydrogenase Adh1, Adh3, and Adh4 null mutant mice. Overlapping roles of Adh1 and Adh4 in ethanol clearance and metabolism of retinol to retinoic acid. (1999). https://pubmed.ncbi.nlm.nih.gov/10358022/ DOI: 10.1074/jbc.274.24.16796","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}