{"id":"9446d7b7-d041-5336-9f34-cb1b90d5ec6d","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-theophylline-1a2","predicate":"metabolizes","statement":"CYP1A2 catalyzed theophylline demethylation and hydroxylation, with high affinity and the highest tested intrinsic clearance to dimethyluric acid.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"b6e63333-f065-54ab-98c4-8d2929dff45f","mechanism_event_label":"Theophylline is a relevant substrate to investigate, but DIM-induced concentration changes were not measured.","subject":{"id":"9b15c13c-a369-5d10-a76a-525e8b19221d","slug":"cyp1a2","display_name":"Human cytochrome P450 1A2","entity_type_key":"protein"},"object":{"id":"544c8ab3-8476-576f-bdae-31cd595a980e","slug":"theophylline","display_name":"Theophylline","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"b6e63333-f065-54ab-98c4-8d2929dff45f","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-theophylline-1a2-event","event_type":"biochemical_relationship","label":"Theophylline is a relevant substrate to investigate, but DIM-induced concentration changes were not measured.","description":"CYP1A2 catalyzed theophylline demethylation and hydroxylation, with high affinity and the highest tested intrinsic clearance to dimethyluric acid.","status":"provisional","compartment":null,"participants":[{"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":0,"notes":""},{"entity":{"id":"544c8ab3-8476-576f-bdae-31cd595a980e","slug":"theophylline","display_name":"Theophylline","entity_type_key":"small_molecule"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/dim-research/7619675.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"0697fc53b8afe8bb59065fc098e9965c7c230ad77823bea7638cd3b8049b04fb\", \"start_char\": 0, \"end_char\": 1842, \"text_sha256\": \"0697fc53b8afe8bb59065fc098e9965c7c230ad77823bea7638cd3b8049b04fb\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Recombinant human enzyme kinetics","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Multiple substrate concentrations","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Substrate concentration changed relative contributions. Not a DIM-theophylline study or an individual dosing rule.","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 CYP isoforms expressed in lymphoblastoid cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Theophylline is a relevant substrate to investigate, but DIM-induced concentration changes were not measured.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[dim-p7619675] Metabolism of theophylline by cDNA-expressed human cytochromes P-450. (1995). https://pubmed.ncbi.nlm.nih.gov/7619675/ DOI: 10.1111/j.1365-2125.1995.tb04455.x","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Theophylline metabolism","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"f77aa0ac-fcce-5216-b14c-425a294ad27c","evidence_kind":"source_excerpt","locator":"Lines 766-777","start_line":766,"end_line":777,"excerpt":"### dim-theophylline-1a2\nCYP1A2 catalyzed theophylline demethylation and hydroxylation, with high affinity and the highest tested intrinsic clearance to dimethyluric acid.\nCondition category: normal\nnutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Theophylline is a relevant substrate to investigate, but DIM-induced concentration changes were not measured.\norganism: Human CYP isoforms expressed in lymphoblastoid cells\ntissue_or_cell_type: Theophylline metabolism\nexperimental_model: Recombinant human enzyme kinetics\nlimitations: Substrate concentration changed relative contributions. Not a DIM-theophylline study or an individual dosing rule.\nexposure: Multiple substrate concentrations\nevidence_span: {\"source_cache\": \"artifacts/dim-research/7619675.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"0697fc53b8afe8bb59065fc098e9965c7c230ad77823bea7638cd3b8049b04fb\", \"start_char\": 0, \"end_char\": 1842, \"text_sha256\": \"0697fc53b8afe8bb59065fc098e9965c7c230ad77823bea7638cd3b8049b04fb\"}\n[dim-p7619675] Metabolism of theophylline by cDNA-expressed human cytochromes P-450. (1995). https://pubmed.ncbi.nlm.nih.gov/7619675/ DOI: 10.1111/j.1365-2125.1995.tb04455.x","model_system":"Recombinant human enzyme kinetics","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [dim-p7619675] Metabolism of theophylline by cDNA-expressed human cytochromes P-450. (1995). https://pubmed.ncbi.nlm.nih.gov/7619675/ DOI: 10.1111/j.1365-2125.1995.tb04455.x","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"b6d70682-97f9-5893-a03c-f9f88836033c","stable_key":"import-182336c6-ed36-5ec6-8a09-25c31096262e","title":"Diindolylmethane (DIM): formation, receptor signaling, metabolism and drug interactions (2026-09-17)","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":"31e14060de904976d2f5d439f2bc9c8a99a72d34626c562c78429025e050d404","revision_id":"611094c1-a9cf-5b9b-b255-ac70b571696a","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}