{"id":"fbc8a163-c9dc-59e5-bbf7-9e955a37e0ed","stable_key":"548ab9d6-3a9b-5bed-879c-17d03813b636:b2-gsr-flavin-disulfide-relay","predicate":"supports-redox-relay-in","statement":"The GSR catalytic cycle transfers reducing equivalents from flavin to the Cys58-Cys63 active-site disulfide before glutathione-disulfide reduction.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"b644520a-bd73-56ca-b4a7-c8e1e646b4b3","mechanism_event_label":"FAD relays electrons through enzyme cysteines.","subject":{"id":"e2cd7179-f218-54e8-9ce9-7a836ae35fac","slug":"fad","display_name":"FAD","entity_type_key":"small_molecule"},"object":{"id":"ae04c12f-c0ac-5c8d-9ee2-76e58156d105","slug":"gsr","display_name":"Glutathione reductase / GSR","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"b644520a-bd73-56ca-b4a7-c8e1e646b4b3","stable_key":"548ab9d6-3a9b-5bed-879c-17d03813b636:b2-gsr-flavin-disulfide-relay-event","event_type":"biochemical_relationship","label":"FAD relays electrons through enzyme cysteines.","description":"The GSR catalytic cycle transfers reducing equivalents from flavin to the Cys58-Cys63 active-site disulfide before glutathione-disulfide reduction.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"e2cd7179-f218-54e8-9ce9-7a836ae35fac","slug":"fad","display_name":"FAD","entity_type_key":"small_molecule"},"role":"bound redox mediator","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"ae04c12f-c0ac-5c8d-9ee2-76e58156d105","slug":"gsr","display_name":"Glutathione reductase / GSR","entity_type_key":"protein"},"role":"Cys58-Cys63 redox center","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"B2-derived cofactor bridges NADPH and the glutathione system.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"evidence_location","value_text":"Results: NADPH binding; Fig 1 consensus cycle; GSH/GSSG complexes","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Purified-enzyme assay","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Mechanism integrates natural-substrate structures with prior kinetic work; transient intermediates were not all directly trapped here.","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":"Homo sapiens","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"FAD relays electrons through enzyme cysteines.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[berkholz2008] Catalytic cycle of human glutathione reductase near 1 A resolution. (2008). https://pubmed.ncbi.nlm.nih.gov/18638483/ DOI: 10.1016/j.jmb.2008.06.083","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified human GSR","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"7435e5fc-faed-53d9-b485-713fe9b197bd","evidence_kind":"source_excerpt","locator":"Lines 1318-1330","start_line":1318,"end_line":1330,"excerpt":"### b2-gsr-flavin-disulfide-relay\nThe GSR catalytic cycle transfers reducing equivalents from flavin to the Cys58-Cys63 active-site disulfide before glutathione-disulfide reduction.\nCondition category: normal\nnutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: FAD relays electrons through enzyme cysteines.\norganism: Homo sapiens\ntissue_or_cell_type: Purified human GSR\nexperimental_model: Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls.\nlimitations: Mechanism integrates natural-substrate structures with prior kinetic work; transient intermediates were not all directly trapped here.\nexposure: Purified-enzyme assay\ncross_nutrient: B2-derived cofactor bridges NADPH and the glutathione system.\nevidence_location: Results: NADPH binding; Fig 1 consensus cycle; GSH/GSSG complexes\n[berkholz2008] Catalytic cycle of human glutathione reductase near 1 A resolution. (2008). https://pubmed.ncbi.nlm.nih.gov/18638483/ DOI: 10.1016/j.jmb.2008.06.083","model_system":"Purified human glutathione reductase crystals with natural substrates, 0.95-1.1-A resolution, chemically reduced controls.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [berkholz2008] Catalytic cycle of human glutathione reductase near 1 A resolution. (2008). https://pubmed.ncbi.nlm.nih.gov/18638483/ DOI: 10.1016/j.jmb.2008.06.083","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. 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