{"id":"95c4b2dc-5f5e-5cfa-bd32-384e982fc3f2","stable_key":"5d8e27d8-6a74-5560-827f-3f90908bbc34:ala-lipt1-enzyme-partial-response","predicate":"has_limited_effect_on","statement":"In those LIPT1-deficient fibroblasts, PDH activity increased only moderately, OGDH showed no increase, and the leucine-flux assay showed no BCKDH rescue.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"3398ed51-02d8-584d-9948-f80578db7593","mechanism_event_label":"A lower lactate measurement did not mean all affected enzyme systems were repaired.","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":"3398ed51-02d8-584d-9948-f80578db7593","stable_key":"5d8e27d8-6a74-5560-827f-3f90908bbc34:ala-lipt1-enzyme-partial-response-event","event_type":"biochemical_relationship","label":"A lower lactate measurement did not mean all affected enzyme systems were repaired.","description":"In those LIPT1-deficient fibroblasts, PDH activity increased only moderately, OGDH showed no increase, and the leucine-flux assay showed no BCKDH rescue.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"8d8cf36b-d1f4-57eb-8ce2-798d6f3c30b9","slug":"oxoglutarate-dehydrogenase-complex","display_name":"2-Oxoglutarate dehydrogenase complex","entity_type_key":"protein_complex"},"role":"unrestored_complex","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"99e4447f-bc64-5044-bbc8-cbba58545262","slug":"dbt","display_name":"Dihydrolipoyl branched-chain transacylase / DBT","entity_type_key":"protein"},"role":"bckdh_component","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"a044660b-d63d-5adb-9b1f-ac9c2b8901bd","slug":"lipt1","display_name":"Human lipoyl amidotransferase / LIPT1","entity_type_key":"protein"},"role":"impaired_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":"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":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/24341803.fulltext.txt\", \"locator\": \"Exact primary full-text span; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"44f3fc89f065e58c1deb82f02c93a3654504f002fbc051d00a7703d3fbe6764b\", \"start_char\": 19977, \"end_char\": 20689, \"text_sha256\": \"3a495a2251965512793b341794c86b5caedc8525754344b8bba51281e7802a79\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"LIPT1 patient fibroblasts with supplementation and genetic complementation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Lipoic acid 10 or 100 micromolar for three weeks","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Partial biochemical changes do not establish restored lipoylation or clinical efficacy. Historical pathway speculation is not imported as current enzymology.","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":"A lower lactate measurement did not mean all affected enzyme systems were repaired.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ala-p24341803] Mutations in human lipoyltransferase gene LIPT1 cause a Leigh disease with secondary deficiency for pyruvate and alpha-ketoglutarate dehydrogenase. (2013). https://pubmed.ncbi.nlm.nih.gov/24341803/ DOI: 10.1186/1750-1172-8-192","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Patient and control fibroblasts","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":"86b1aaba-9ead-56aa-a4f1-2111e2924ca3","evidence_kind":"source_excerpt","locator":"Lines 494-505","start_line":494,"end_line":505,"excerpt":"### ala-lipt1-enzyme-partial-response\nIn those LIPT1-deficient fibroblasts, PDH activity increased only moderately, OGDH showed no increase, and the leucine-flux assay showed no BCKDH rescue.\nCondition category: machinery_impairment\nnutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A lower lactate measurement did not mean all affected enzyme systems were repaired.\norganism: Human\ntissue_or_cell_type: Patient and control fibroblasts\nexperimental_model: LIPT1 patient fibroblasts with supplementation and genetic complementation\nlimitations: Partial biochemical changes do not establish restored lipoylation or clinical efficacy. Historical pathway speculation is not imported as current enzymology.\nexposure: Lipoic acid 10 or 100 micromolar for three weeks\nevidence_span: {\"source_cache\": \"artifacts/ala-research/24341803.fulltext.txt\", \"locator\": \"Exact primary full-text span; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"44f3fc89f065e58c1deb82f02c93a3654504f002fbc051d00a7703d3fbe6764b\", \"start_char\": 19977, \"end_char\": 20689, \"text_sha256\": \"3a495a2251965512793b341794c86b5caedc8525754344b8bba51281e7802a79\"}\n[ala-p24341803] Mutations in human lipoyltransferase gene LIPT1 cause a Leigh disease with secondary deficiency for pyruvate and alpha-ketoglutarate dehydrogenase. (2013). https://pubmed.ncbi.nlm.nih.gov/24341803/ DOI: 10.1186/1750-1172-8-192","model_system":"LIPT1 patient fibroblasts with supplementation and genetic complementation","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [ala-p24341803] Mutations in human lipoyltransferase gene LIPT1 cause a Leigh disease with secondary deficiency for pyruvate and alpha-ketoglutarate dehydrogenase. 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