{"id":"41b7c477-f2c0-5a85-96b9-0140c7648028","stable_key":"5d8e27d8-6a74-5560-827f-3f90908bbc34:ala-lipt2-supplement-no-rescue","predicate":"did_not_restore","statement":"Lipoic acid supplementation did not improve the reported clinical course or restore deficient PDH, OGDH and leucine-catabolic function in LIPT2-deficient fibroblasts.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"neutral","is_public":true,"mechanism_event_id":"3e317744-1f77-5643-8c55-6630b81d39d7","mechanism_event_label":"More free lipoic acid did not bypass the broken assembly step.","subject":{"id":"ab091982-3acb-5a87-80fb-85dfe292c1e0","slug":"lipoic-acid","display_name":"Lipoic acid","entity_type_key":"small_molecule"},"object":{"id":"6d908873-0745-523a-96bf-9cf25bda2676","slug":"pyruvate-dehydrogenase-complex","display_name":"Human pyruvate dehydrogenase complex","entity_type_key":"protein_complex"},"evidence_count":1,"mechanism_event":{"id":"3e317744-1f77-5643-8c55-6630b81d39d7","stable_key":"5d8e27d8-6a74-5560-827f-3f90908bbc34:ala-lipt2-supplement-no-rescue-event","event_type":"biochemical_relationship","label":"More free lipoic acid did not bypass the broken assembly step.","description":"Lipoic acid supplementation did not improve the reported clinical course or restore deficient PDH, OGDH and leucine-catabolic function in LIPT2-deficient fibroblasts.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"1bd56cad-1080-5586-bcd3-3c9d626443eb","slug":"lipt2","display_name":"Human octanoyltransferase / LIPT2","entity_type_key":"protein"},"role":"impaired_machinery","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"8d8cf36b-d1f4-57eb-8ce2-798d6f3c30b9","slug":"oxoglutarate-dehydrogenase-complex","display_name":"2-Oxoglutarate dehydrogenase complex","entity_type_key":"protein_complex"},"role":"affected_complex","stoichiometry":null,"state_label":"","sequence_order":1,"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":2,"notes":""},{"entity":{"id":"6d908873-0745-523a-96bf-9cf25bda2676","slug":"pyruvate-dehydrogenase-complex","display_name":"Human pyruvate dehydrogenase complex","entity_type_key":"protein_complex"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":3,"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/28757203.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"a03fbeaf7603f02004672c4068bb20fba9021a7662964565bafe62ccecb0ee1f\", \"start_char\": 0, \"end_char\": 1639, \"text_sha256\": \"a03fbeaf7603f02004672c4068bb20fba9021a7662964565bafe62ccecb0ee1f\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Three affected children from two families and patient-derived fibroblasts","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Biallelic LIPT2 variants; wild-type gene rescue and lipoic acid supplementation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Rare inherited disease; not evidence for common dietary lipoic-acid deficiency.","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":"More free lipoic acid did not bypass the broken assembly step.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ala-p28757203] Biallelic Mutations in LIPT2 Cause a Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy. (2017). https://pubmed.ncbi.nlm.nih.gov/28757203/ DOI: 10.1016/j.ajhg.2017.07.001","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Patient cells and clinical phenotype","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":"014f5e9f-105a-5ac7-a9f8-e71059d69fe9","evidence_kind":"source_excerpt","locator":"Lines 442-453","start_line":442,"end_line":453,"excerpt":"### ala-lipt2-supplement-no-rescue\nLipoic acid supplementation did not improve the reported clinical course or restore deficient PDH, OGDH and leucine-catabolic function in LIPT2-deficient fibroblasts.\nCondition category: machinery_impairment\nnutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: More free lipoic acid did not bypass the broken assembly step.\norganism: Human\ntissue_or_cell_type: Patient cells and clinical phenotype\nexperimental_model: Three affected children from two families and patient-derived fibroblasts\nlimitations: Rare inherited disease; not evidence for common dietary lipoic-acid deficiency.\nexposure: Biallelic LIPT2 variants; wild-type gene rescue and lipoic acid supplementation\nevidence_span: {\"source_cache\": \"artifacts/ala-research/28757203.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"a03fbeaf7603f02004672c4068bb20fba9021a7662964565bafe62ccecb0ee1f\", \"start_char\": 0, \"end_char\": 1639, \"text_sha256\": \"a03fbeaf7603f02004672c4068bb20fba9021a7662964565bafe62ccecb0ee1f\"}\n[ala-p28757203] Biallelic Mutations in LIPT2 Cause a Mitochondrial Lipoylation Defect Associated with Severe Neonatal Encephalopathy. 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