{"id":"8e710d33-3cfb-55dd-9e02-80502a48f6ae","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-melatonin-1a2","predicate":"hydroxylates","statement":"CYP1A2 was the principal high-affinity, but not exclusive, enzyme for melatonin 6-hydroxylation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"8ca5f59c-51ab-5c95-98f4-09e9e9187bfe","mechanism_event_label":"Melatonin shares the enzyme; a DIM effect on sleep cannot be read directly from this edge.","subject":{"id":"9b15c13c-a369-5d10-a76a-525e8b19221d","slug":"cyp1a2","display_name":"Human cytochrome P450 1A2","entity_type_key":"protein"},"object":{"id":"0f0bc1f1-d18d-5652-bc1d-98f61f7ab65c","slug":"melatonin","display_name":"Melatonin","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"8ca5f59c-51ab-5c95-98f4-09e9e9187bfe","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-melatonin-1a2-event","event_type":"biochemical_relationship","label":"Melatonin shares the enzyme; a DIM effect on sleep cannot be read directly from this edge.","description":"CYP1A2 was the principal high-affinity, but not exclusive, enzyme for melatonin 6-hydroxylation.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"71a6f429-bc05-5ab0-86bd-75bec8db8ccf","slug":"6-hydroxymelatonin","display_name":"6-Hydroxymelatonin","entity_type_key":"small_molecule"},"role":"product","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"9b15c13c-a369-5d10-a76a-525e8b19221d","slug":"cyp1a2","display_name":"Human cytochrome P450 1A2","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"0f0bc1f1-d18d-5652-bc1d-98f61f7ab65c","slug":"melatonin","display_name":"Melatonin","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/dim-research/11317475.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"503f4e9d299c6c978aa1e867a32cdc7b4f5c191290b74415f0f152d3b2f0d87d\", \"start_char\": 0, \"end_char\": 1580, \"text_sha256\": \"503f4e9d299c6c978aa1e867a32cdc7b4f5c191290b74415f0f152d3b2f0d87d\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Human microsomes, expressed enzymes and inhibition assays","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Substrate range 1-1000 micromolar","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"In-vitro pathway identification; no DIM coadministration, sleep outcome or proof that DIM lowers nighttime melatonin.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"dim","display_name":"3,3'-Diindolylmethane / DIM","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human liver CYP systems","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Melatonin shares the enzyme; a DIM effect on sleep cannot be read directly from this edge.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[dim-p11317475] Cytochrome P450 isoforms involved in melatonin metabolism in human liver microsomes. (2001). https://pubmed.ncbi.nlm.nih.gov/11317475/ DOI: 10.1007/s002280000245","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Melatonin 6-hydroxylation","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"50025bd3-c730-5617-8831-6f8a63fd81f7","evidence_kind":"source_excerpt","locator":"Lines 818-829","start_line":818,"end_line":829,"excerpt":"### dim-melatonin-1a2\nCYP1A2 was the principal high-affinity, but not exclusive, enzyme for melatonin 6-hydroxylation.\nCondition category: normal\nnutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Melatonin shares the enzyme; a DIM effect on sleep cannot be read directly from this edge.\norganism: Human liver CYP systems\ntissue_or_cell_type: Melatonin 6-hydroxylation\nexperimental_model: Human microsomes, expressed enzymes and inhibition assays\nlimitations: In-vitro pathway identification; no DIM coadministration, sleep outcome or proof that DIM lowers nighttime melatonin.\nexposure: Substrate range 1-1000 micromolar\nevidence_span: {\"source_cache\": \"artifacts/dim-research/11317475.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"503f4e9d299c6c978aa1e867a32cdc7b4f5c191290b74415f0f152d3b2f0d87d\", \"start_char\": 0, \"end_char\": 1580, \"text_sha256\": \"503f4e9d299c6c978aa1e867a32cdc7b4f5c191290b74415f0f152d3b2f0d87d\"}\n[dim-p11317475] Cytochrome P450 isoforms involved in melatonin metabolism in human liver microsomes. 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