{"id":"f9829b45-4e3f-5bef-8d08-fc9acf7425e6","stable_key":"5d8e27d8-6a74-5560-827f-3f90908bbc34:ala-variant-lipoate-no-rescue","predicate":"did_not_correct","statement":"Neither lipoate nor mitochondrially targeted lipoate corrected the studied cellular lipoylation deficiency.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"a15ebdd9-a70b-5b77-b4e3-dd799491e558","mechanism_event_label":"Delivering the molecule nearer mitochondria was still insufficient in these models.","subject":{"id":"ab091982-3acb-5a87-80fb-85dfe292c1e0","slug":"lipoic-acid","display_name":"Lipoic acid","entity_type_key":"small_molecule"},"object":{"id":"a545cda4-692b-5513-a8f3-71c0afb0736c","slug":"mitochondrial-protein-lipoylation","display_name":"Mitochondrial protein lipoylation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"a15ebdd9-a70b-5b77-b4e3-dd799491e558","stable_key":"5d8e27d8-6a74-5560-827f-3f90908bbc34:ala-variant-lipoate-no-rescue-event","event_type":"biochemical_relationship","label":"Delivering the molecule nearer mitochondria was still insufficient in these models.","description":"Neither lipoate nor mitochondrially targeted lipoate corrected the studied cellular lipoylation deficiency.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"f9fc9417-ca4f-5e0c-b01d-60b337493d34","slug":"lias","display_name":"Lipoic acid synthetase / LIAS","entity_type_key":"protein"},"role":"affected_machinery","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"b8eb1321-0943-5bb5-8006-9ab3917ba22e","slug":"bola3","display_name":"Human BOLA3","entity_type_key":"protein"},"role":"affected_machinery","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"4d72b0cf-da5e-5f9e-9da8-0ee9082ec1a3","slug":"glrx5","display_name":"Human mitochondrial glutaredoxin 5 / GLRX5","entity_type_key":"protein"},"role":"affected_machinery","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"ab091982-3acb-5a87-80fb-85dfe292c1e0","slug":"lipoic-acid","display_name":"Lipoic acid","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"a545cda4-692b-5513-a8f3-71c0afb0736c","slug":"mitochondrial-protein-lipoylation","display_name":"Mitochondrial protein lipoylation","entity_type_key":"cellular_process"},"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/ala-research/24334290.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"2d6f134f9da5ac532fac9c58757e80a0b51c9912f8ddbec39eb81d1e81ccbfb2\", \"start_char\": 0, \"end_char\": 2342, \"text_sha256\": \"2d6f134f9da5ac532fac9c58757e80a0b51c9912f8ddbec39eb81d1e81ccbfb2\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Variant nonketotic hyperglycinemia cohort and cell complementation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"LIAS, BOLA3 or GLRX5 variants; lipoate and mitochondrially targeted lipoate in cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Phenotypes varied; respiratory-chain function was preserved in this series, unlike some other Fe-S disorders.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"lipoic-acid","display_name":"Lipoic acid","entity_type_key":"small_molecule"}},{"dimension":"organism","value_text":"Human","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Delivering the molecule nearer mitochondria was still insufficient in these models.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ala-p24334290] Variant non ketotic hyperglycinemia is caused by mutations in LIAS, BOLA3 and the novel gene GLRX5. 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