{"id":"eb840980-e2c0-562a-8d8b-45fe7514b0fe","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-por-fmn-loss","predicate":"impaired_fmn_binding_limits","statement":"POR Y181D lacked bound FMN and poorly supported CYP1A2-catalyzed reactions despite retaining FAD binding and NADPH utilization.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"ff3e7da4-c98b-5787-b53b-04434193941a","mechanism_event_label":"Inducing an enzyme is not enough if its electron-supply machinery fails.","subject":{"id":"fe139c0e-8e78-562e-921b-5696200d7491","slug":"por-y181d","display_name":"Human POR Y181D variant","entity_type_key":"protein"},"object":{"id":"9b15c13c-a369-5d10-a76a-525e8b19221d","slug":"cyp1a2","display_name":"Human cytochrome P450 1A2","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"ff3e7da4-c98b-5787-b53b-04434193941a","stable_key":"182336c6-ed36-5ec6-8a09-25c31096262e:dim-por-fmn-loss-event","event_type":"biochemical_relationship","label":"Inducing an enzyme is not enough if its electron-supply machinery fails.","description":"POR Y181D lacked bound FMN and poorly supported CYP1A2-catalyzed reactions despite retaining FAD binding and NADPH utilization.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"d3eacf85-1a35-546d-bd30-161474dd9691","slug":"fmn","display_name":"Flavin mononucleotide","entity_type_key":"small_molecule"},"role":"impaired_cofactor_binding","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"e2cd7179-f218-54e8-9ce9-7a836ae35fac","slug":"fad","display_name":"FAD","entity_type_key":"small_molecule"},"role":"retained_binding","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"4aba2a5e-8d06-5304-bb01-c0402b225a94","slug":"nadph","display_name":"NADPH","entity_type_key":"small_molecule"},"role":"retained_utilization","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"fe139c0e-8e78-562e-921b-5696200d7491","slug":"por-y181d","display_name":"Human POR Y181D variant","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"9b15c13c-a369-5d10-a76a-525e8b19221d","slug":"cyp1a2","display_name":"Human cytochrome P450 1A2","entity_type_key":"protein"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":4,"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/dim-research/19884324.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"3f702cc9af1528241d8572b8bcafc23dacb5ed3cacf6bb77403e8aa40d21a214\", \"start_char\": 0, \"end_char\": 1738, \"text_sha256\": \"3f702cc9af1528241d8572b8bcafc23dacb5ed3cacf6bb77403e8aa40d21a214\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Recombinant protein and engineered bacterial coexpression","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"POR mutation and added FMN","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"In-vitro rescue of one mutant; not a dietary-riboflavin deficiency experiment or evidence that FMN reverses a DIM-drug interaction.","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 POR Y181D and human CYP1A2 in engineered systems","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Inducing an enzyme is not enough if its electron-supply machinery fails.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[dim-p19884324] Human cytochrome P450 oxidoreductase deficiency caused by the Y181D mutation: molecular consequences and rescue of defect. (2010). https://pubmed.ncbi.nlm.nih.gov/19884324/ DOI: 10.1124/dmd.109.030445","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"FMN-dependent electron transfer","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":"655d5188-8f0f-5fc1-a955-c4436becfea9","evidence_kind":"source_excerpt","locator":"Lines 272-283","start_line":272,"end_line":283,"excerpt":"### dim-por-fmn-loss\nPOR Y181D lacked bound FMN and poorly supported CYP1A2-catalyzed reactions despite retaining FAD binding and NADPH utilization.\nCondition category: machinery_impairment\nnutrient_topic: Diindolylmethane (DIM) research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Inducing an enzyme is not enough if its electron-supply machinery fails.\norganism: Human POR Y181D and human CYP1A2 in engineered systems\ntissue_or_cell_type: FMN-dependent electron transfer\nexperimental_model: Recombinant protein and engineered bacterial coexpression\nlimitations: In-vitro rescue of one mutant; not a dietary-riboflavin deficiency experiment or evidence that FMN reverses a DIM-drug interaction.\nexposure: POR mutation and added FMN\nevidence_span: {\"source_cache\": \"artifacts/dim-research/19884324.abstract.txt\", \"locator\": \"Primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"3f702cc9af1528241d8572b8bcafc23dacb5ed3cacf6bb77403e8aa40d21a214\", \"start_char\": 0, \"end_char\": 1738, \"text_sha256\": \"3f702cc9af1528241d8572b8bcafc23dacb5ed3cacf6bb77403e8aa40d21a214\"}\n[dim-p19884324] Human cytochrome P450 oxidoreductase deficiency caused by the Y181D mutation: molecular consequences and rescue of defect. (2010). https://pubmed.ncbi.nlm.nih.gov/19884324/ DOI: 10.1124/dmd.109.030445","model_system":"Recombinant protein and engineered bacterial coexpression","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [dim-p19884324] Human cytochrome P450 oxidoreductase deficiency caused by the Y181D mutation: molecular consequences and rescue of defect. (2010). https://pubmed.ncbi.nlm.nih.gov/19884324/ DOI: 10.1124/dmd.109.030445","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. 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