{"id":"22115ab1-35e5-524c-b247-c44a163c5f51","stable_key":"548ab9d6-3a9b-5bed-879c-17d03813b636:b2-met-dld-g101del-fad-retention","predicate":"reduces-cofactor-retention","statement":"Human DLD G101del retained about 0.07 FAD per monomer in the recombinant preparation; size-exclusion analysis also indicated loss of its normal dimeric assembly.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"negative","is_public":true,"mechanism_event_id":"22b4c32c-ac7e-55c0-aed4-c6ad25bfa257","mechanism_event_label":"A different DLD alteration disrupted both flavin retention and protein assembly.","subject":{"id":"97d63fed-c568-5526-875f-314fb17da51f","slug":"dld-g101del","display_name":"Human DLD Gly101 deletion","entity_type_key":"protein_state"},"object":{"id":"e2cd7179-f218-54e8-9ce9-7a836ae35fac","slug":"fad","display_name":"FAD","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"22b4c32c-ac7e-55c0-aed4-c6ad25bfa257","stable_key":"548ab9d6-3a9b-5bed-879c-17d03813b636:b2-met-dld-g101del-fad-retention-event","event_type":"biochemical_relationship","label":"A different DLD alteration disrupted both flavin retention and protein assembly.","description":"Human DLD G101del retained about 0.07 FAD per monomer in the recombinant preparation; 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unverified.","entity":null},{"dimension":"evidence_spans","value_text":"[{\"source_bundle\": \"artifacts/riboflavin_metabolism_sources.json\", \"source_key\": \"PMC10341545\", \"locator\": \"XML .//body//p\", \"paragraph_index\": 5, \"char_start\": 0, \"char_end\": 502, \"evidence_access\": \"full-text\"}, {\"source_bundle\": \"artifacts/riboflavin_metabolism_sources.json\", \"source_key\": \"PMC10341545\", \"locator\": \"XML .//body//p\", \"paragraph_index\": 6, \"char_start\": 0, \"char_end\": 1435, \"evidence_access\": \"full-text\"}]","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Recombinant human DLD variants expressed in E. coli BL21(DE3), FAD quantification, activity, chromatography and crystallography.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"G101del mutagenesis; FAD quantification and calibrated size exclusion.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Low expression and preparation heterogeneity were reported; no riboflavin-rescue experiment.","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":"A different DLD alteration disrupted both flavin retention and protein assembly.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[szabo-2023-dld-variants] Structural and Biochemical Investigation of Selected Pathogenic Mutants of the Human Dihydrolipoamide Dehydrogenase (2023). https://pubmed.ncbi.nlm.nih.gov/37446004/ DOI: 10.3390/ijms241310826","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified recombinant DLD","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":"c9c39050-f497-54f3-af87-e486b883d5d5","evidence_kind":"source_excerpt","locator":"Lines 861-872","start_line":861,"end_line":872,"excerpt":"### b2-met-dld-g101del-fad-retention\nHuman DLD G101del retained about 0.07 FAD per monomer in the recombinant preparation; size-exclusion analysis also indicated loss of its normal dimeric assembly.\nCondition category: machinery_impairment\nnutrient_topic: Riboflavin research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A different DLD alteration disrupted both flavin retention and protein assembly.\norganism: Homo sapiens\ntissue_or_cell_type: Purified recombinant DLD\nexperimental_model: Recombinant human DLD variants expressed in E. coli BL21(DE3), FAD quantification, activity, chromatography and crystallography.\nlimitations: Low expression and preparation heterogeneity were reported; no riboflavin-rescue experiment.\nexposure: G101del mutagenesis; FAD quantification and calibrated size exclusion.\nevidence_spans: [{\"source_bundle\": \"artifacts/riboflavin_metabolism_sources.json\", \"source_key\": \"PMC10341545\", \"locator\": \"XML .//body//p\", \"paragraph_index\": 5, \"char_start\": 0, \"char_end\": 502, \"evidence_access\": \"full-text\"}, {\"source_bundle\": \"artifacts/riboflavin_metabolism_sources.json\", \"source_key\": \"PMC10341545\", \"locator\": \"XML .//body//p\", \"paragraph_index\": 6, \"char_start\": 0, \"char_end\": 1435, \"evidence_access\": \"full-text\"}]\n[szabo-2023-dld-variants] Structural and Biochemical Investigation of Selected Pathogenic Mutants of the Human Dihydrolipoamide Dehydrogenase (2023). https://pubmed.ncbi.nlm.nih.gov/37446004/ DOI: 10.3390/ijms241310826","model_system":"Recombinant human DLD variants expressed in E. coli BL21(DE3), FAD quantification, activity, chromatography and crystallography.","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [szabo-2023-dld-variants] Structural and Biochemical Investigation of Selected Pathogenic Mutants of the Human Dihydrolipoamide Dehydrogenase (2023). https://pubmed.ncbi.nlm.nih.gov/37446004/ DOI: 10.3390/ijms241310826","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}