{"id":"a1eee14d-9726-5eb0-9fc2-02778e8968c5","stable_key":"548ab9d6-3a9b-5bed-879c-17d03813b636:b2-met-complex-i-reductive-fmn-loss","predicate":"promotes-cofactor-dissociation","statement":"NADH plus respiratory blockade at alkaline pH caused time-dependent activity loss consistent with reversible FMN dissociation from bovine membrane-bound complex I.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"3dcf56eb-441d-5f78-b737-6b1dcc4e2103","mechanism_event_label":"An unusually reduced, alkaline laboratory environment loosened the enzyme-bound flavin.","subject":{"id":"9fbf2e03-16a9-5ca7-965c-0bfc07ca24da","slug":"nadh","display_name":"NADH","entity_type_key":"small_molecule"},"object":{"id":"f67ac698-de2e-55f5-8975-305eaadbb751","slug":"respiratory-complex-i","display_name":"Mitochondrial respiratory complex I","entity_type_key":"protein_complex"},"evidence_count":1,"mechanism_event":{"id":"3dcf56eb-441d-5f78-b737-6b1dcc4e2103","stable_key":"548ab9d6-3a9b-5bed-879c-17d03813b636:b2-met-complex-i-reductive-fmn-loss-event","event_type":"biochemical_relationship","label":"An unusually reduced, alkaline laboratory environment loosened the enzyme-bound flavin.","description":"NADH plus respiratory blockade at alkaline pH caused time-dependent activity loss consistent with reversible FMN dissociation from bovine membrane-bound complex I.","status":"provisional","compartment":{"slug":"mitochondria","display_name":"Mitochondria"},"participants":[{"entity":{"id":"d3eacf85-1a35-546d-bd30-161474dd9691","slug":"fmn","display_name":"Flavin mononucleotide","entity_type_key":"small_molecule"},"role":"dissociating cofactor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"9fbf2e03-16a9-5ca7-965c-0bfc07ca24da","slug":"nadh","display_name":"NADH","entity_type_key":"small_molecule"},"role":"experimental reducing substrate","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"f67ac698-de2e-55f5-8975-305eaadbb751","slug":"respiratory-complex-i","display_name":"Mitochondrial respiratory complex I","entity_type_key":"protein_complex"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"machinery_impairment","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null},{"dimension":"evidence_spans","value_text":"[{\"source_bundle\": \"artifacts/riboflavin_metabolism_sources.json\", \"source_key\": \"PMC2440658\", \"locator\": \"HTML article p\", \"paragraph_index\": 11, \"char_start\": 0, \"char_end\": 1107, \"evidence_access\": \"full-text\"}]","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"NADH with rotenone or cyanide, alkaline pH; time-dependent NADH:HAR and NADH:Q1 assays.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Biochemical inference from kinetic/cofactor reconstitution experiments; nonphysiological pH.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Riboflavin research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"riboflavin","display_name":"Riboflavin (vitamin B2)","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Bos taurus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"An unusually reduced, alkaline laboratory environment loosened the enzyme-bound flavin.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[gostimskaya-2007-complex-i-fmn] Reversible dissociation of flavin mononucleotide from the mammalian membrane-bound NADH: ubiquinone oxidoreductase (complex I) (2007). https://pubmed.ncbi.nlm.nih.gov/18037377/ DOI: 10.1016/j.febslet.2007.11.048","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Heart submitochondrial particles","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":"b754c0c3-9245-546e-98e6-e6e8a70d8902","evidence_kind":"source_excerpt","locator":"Lines 583-594","start_line":583,"end_line":594,"excerpt":"### b2-met-complex-i-reductive-fmn-loss\nNADH plus respiratory blockade at alkaline pH caused time-dependent activity loss consistent with reversible FMN dissociation from bovine membrane-bound complex I.\nCondition category: machinery_impairment\nnutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: An unusually reduced, alkaline laboratory environment loosened the enzyme-bound flavin.\norganism: Bos taurus\ntissue_or_cell_type: Heart submitochondrial particles\nexperimental_model: Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution.\nlimitations: Biochemical inference from kinetic/cofactor reconstitution experiments; nonphysiological pH.\nexposure: NADH with rotenone or cyanide, alkaline pH; time-dependent NADH:HAR and NADH:Q1 assays.\nevidence_spans: [{\"source_bundle\": \"artifacts/riboflavin_metabolism_sources.json\", \"source_key\": \"PMC2440658\", \"locator\": \"HTML article p\", \"paragraph_index\": 11, \"char_start\": 0, \"char_end\": 1107, \"evidence_access\": \"full-text\"}]\n[gostimskaya-2007-complex-i-fmn] Reversible dissociation of flavin mononucleotide from the mammalian membrane-bound NADH: ubiquinone oxidoreductase (complex I) (2007). https://pubmed.ncbi.nlm.nih.gov/18037377/ DOI: 10.1016/j.febslet.2007.11.048","model_system":"Bovine heart submitochondrial particles; alkaline reductive inactivation and cofactor reconstitution.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [gostimskaya-2007-complex-i-fmn] Reversible dissociation of flavin mononucleotide from the mammalian membrane-bound NADH: ubiquinone oxidoreductase (complex I) (2007). https://pubmed.ncbi.nlm.nih.gov/18037377/ DOI: 10.1016/j.febslet.2007.11.048","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"4f7c9578-82bf-5e2d-b5c4-72a79fb4f6af","stable_key":"import-548ab9d6-3a9b-5bed-879c-17d03813b636","title":"Riboflavin: mechanisms, deficiency and nutrient 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":"680cb6bc8249877f2410f551807f10d390fdd719014137d7414ba3420e29228d","revision_id":"7a61e299-908d-5372-860b-99ed190f9d7a","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}