{"id":"49965bc8-303d-57ab-9c65-82ecda204877","stable_key":"5d8e27d8-6a74-5560-827f-3f90908bbc34:ala-lipt1-e2-loss","predicate":"loss_impairs","statement":"The LIPT1 case showed deficient PDH and OGDH E2 lipoylation with rescue by wild-type LIPT1.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"590a8d8e-0011-545e-9fb4-c2727dbeef40","mechanism_event_label":"The cofactor was not reaching the dehydrogenase machinery.","subject":{"id":"a044660b-d63d-5adb-9b1f-ac9c2b8901bd","slug":"lipt1","display_name":"Human lipoyl amidotransferase / LIPT1","entity_type_key":"protein"},"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":"590a8d8e-0011-545e-9fb4-c2727dbeef40","stable_key":"5d8e27d8-6a74-5560-827f-3f90908bbc34:ala-lipt1-e2-loss-event","event_type":"biochemical_relationship","label":"The cofactor was not reaching the dehydrogenase machinery.","description":"The LIPT1 case showed deficient PDH and OGDH E2 lipoylation with rescue by wild-type LIPT1.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"12e22bc4-4bc8-5a45-87bc-9274656e9dab","slug":"dlat","display_name":"Dihydrolipoyl acetyltransferase / DLAT","entity_type_key":"protein"},"role":"affected_acceptor","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"6d9c0f10-8013-5379-bc6f-d51367718dec","slug":"dlst","display_name":"DLST","entity_type_key":"protein"},"role":"affected_acceptor","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":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"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":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/24256811.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"57599dd35c58b21d16f2a5955ea667ec8211ab129ee7d0b639b31f18f0976eb2\", \"start_char\": 0, \"end_char\": 1749, \"text_sha256\": \"57599dd35c58b21d16f2a5955ea667ec8211ab129ee7d0b639b31f18f0976eb2\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Affected patient, biochemical testing and complementation","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Compound-heterozygous LIPT1 variants","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Single rare inherited case; enzyme deficits are not interchangeable with nutritional 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":"The cofactor was not reaching the dehydrogenase machinery.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[ala-p24256811] Mutations in the lipoyltransferase LIPT1 gene cause a fatal disease associated with a specific lipoylation defect of the 2-ketoacid dehydrogenase complexes. (2014). https://pubmed.ncbi.nlm.nih.gov/24256811/ DOI: 10.1093/hmg/ddt585","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Patient-derived cells","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":"15275b01-e744-5a4f-9d51-22cf8e1c14fb","evidence_kind":"source_excerpt","locator":"Lines 455-466","start_line":455,"end_line":466,"excerpt":"### ala-lipt1-e2-loss\nThe LIPT1 case showed deficient PDH and OGDH E2 lipoylation with rescue by wild-type LIPT1.\nCondition category: machinery_impairment\nnutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The cofactor was not reaching the dehydrogenase machinery.\norganism: Human\ntissue_or_cell_type: Patient-derived cells\nexperimental_model: Affected patient, biochemical testing and complementation\nlimitations: Single rare inherited case; enzyme deficits are not interchangeable with nutritional deficiency.\nexposure: Compound-heterozygous LIPT1 variants\nevidence_span: {\"source_cache\": \"artifacts/ala-research/24256811.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"57599dd35c58b21d16f2a5955ea667ec8211ab129ee7d0b639b31f18f0976eb2\", \"start_char\": 0, \"end_char\": 1749, \"text_sha256\": \"57599dd35c58b21d16f2a5955ea667ec8211ab129ee7d0b639b31f18f0976eb2\"}\n[ala-p24256811] Mutations in the lipoyltransferase LIPT1 gene cause a fatal disease associated with a specific lipoylation defect of the 2-ketoacid dehydrogenase complexes. 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