{"id":"ed0210a9-3ba2-55b5-8e08-7e78d9ce2768","stable_key":"548ab9d6-3a9b-5bed-879c-17d03813b636:b2-met-depletion-dld","predicate":"supports-protein-abundance","statement":"DLD protein abundance decreased in riboflavin-depleted human 143B cells, while many other mitochondrial matrix flavoproteins did not decline.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"324e9012-c870-54f8-b027-eadf841078cd","mechanism_event_label":"B2 withdrawal destabilized selected flavoproteins, including the shared DLD enzyme.","subject":{"id":"86eb1eee-a8d1-539c-8c17-0911f69b6f1b","slug":"riboflavin","display_name":"Riboflavin (vitamin B2)","entity_type_key":"small_molecule"},"object":{"id":"640b6164-093b-5297-a6bf-55ac8da852ae","slug":"dld","display_name":"DLD","entity_type_key":"protein"},"evidence_count":1,"mechanism_event":{"id":"324e9012-c870-54f8-b027-eadf841078cd","stable_key":"548ab9d6-3a9b-5bed-879c-17d03813b636:b2-met-depletion-dld-event","event_type":"biochemical_relationship","label":"B2 withdrawal destabilized selected flavoproteins, including the shared DLD enzyme.","description":"DLD protein abundance decreased in riboflavin-depleted human 143B cells, while many other mitochondrial matrix flavoproteins did not decline.","status":"provisional","compartment":{"slug":"mitochondria","display_name":"Mitochondria"},"participants":[{"entity":{"id":"640b6164-093b-5297-a6bf-55ac8da852ae","slug":"dld","display_name":"DLD","entity_type_key":"protein"},"role":"decreased protein","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":"DLD cofactor","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"6d908873-0745-523a-96bf-9cf25bda2676","slug":"pyruvate-dehydrogenase-complex","display_name":"Human pyruvate dehydrogenase complex","entity_type_key":"protein_complex"},"role":"existing B1-linked enzyme system","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"8d8cf36b-d1f4-57eb-8ce2-798d6f3c30b9","slug":"oxoglutarate-dehydrogenase-complex","display_name":"2-Oxoglutarate dehydrogenase complex","entity_type_key":"protein_complex"},"role":"existing B1-linked enzyme system","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"187db168-8028-5ce6-9f8b-4bc61ebad1a0","slug":"thiamine-diphosphate","display_name":"Thiamine diphosphate","entity_type_key":"small_molecule"},"role":"cofactor of upstream E1 reactions","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""},{"entity":{"id":"86eb1eee-a8d1-539c-8c17-0911f69b6f1b","slug":"riboflavin","display_name":"Riboflavin (vitamin B2)","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":5,"notes":""}]},"contexts":[{"dimension":"availability_state","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; 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selective loss must not be generalized to all flavoproteins.","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":"B2 withdrawal destabilized selected flavoproteins, including the shared DLD enzyme.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[curtabbi-2024-fmn-assembly] Regulation of respiratory complex I assembly by FMN cofactor targeting (2024). https://pubmed.ncbi.nlm.nih.gov/38145589/ DOI: 10.1016/j.redox.2023.103001","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"143B cell proteomics","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"trigger_kind","value_text":"nutrient_deficiency","comparator":null,"unit":null,"notes":"Imported condition classification; unverified.","entity":null}],"evidence":[{"id":"bd20632b-48f8-5e42-8955-6c470f42e0f7","evidence_kind":"source_excerpt","locator":"Lines 622-634","start_line":622,"end_line":634,"excerpt":"### b2-met-depletion-dld\nDLD protein abundance decreased in riboflavin-depleted human 143B cells, while many other mitochondrial matrix flavoproteins did not decline.\nCondition category: nutrient_deficiency\nnutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: B2 withdrawal destabilized selected flavoproteins, including the shared DLD enzyme.\norganism: Homo sapiens\ntissue_or_cell_type: 143B cell proteomics\nexperimental_model: Human 143B cells and mouse adult fibroblasts, riboflavin-free medium and separate DPI interventions.\nlimitations: No direct PDH/OGDH flux or thiamine-response experiment; selective loss must not be generalized to all flavoproteins.\nexposure: Riboflavin-free medium compared with matched replete medium.\ncross_nutrient: Connects B2-dependent DLD abundance to the canonical B1-dependent mitochondrial complexes; this study does not demonstrate failure of thiamine treatment.\nevidence_spans: [{\"source_bundle\": \"artifacts/riboflavin_metabolism_sources.json\", \"source_key\": \"PMC10767280\", \"locator\": \"XML .//body//p\", \"paragraph_index\": 58, \"char_start\": 0, \"char_end\": 905, \"evidence_access\": \"full-text\"}]\n[curtabbi-2024-fmn-assembly] Regulation of respiratory complex I assembly by FMN cofactor targeting (2024). https://pubmed.ncbi.nlm.nih.gov/38145589/ DOI: 10.1016/j.redox.2023.103001","model_system":"Human 143B cells and mouse adult fibroblasts, riboflavin-free medium and separate DPI interventions.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [curtabbi-2024-fmn-assembly] Regulation of respiratory complex I assembly by FMN cofactor targeting (2024). https://pubmed.ncbi.nlm.nih.gov/38145589/ DOI: 10.1016/j.redox.2023.103001","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}