{"id":"72ef8c97-fcda-53ee-abc1-37d090953d9c","stable_key":"5d8e27d8-6a74-5560-827f-3f90908bbc34:ala-glrx5-glycine-failure","predicate":"defect_associates_with","statement":"GLRX5-associated cases showed deficient protein lipoylation and glycine-cleavage activity with elevated glycine.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"b3342e73-d122-5558-b42f-068e48b6db15","mechanism_event_label":"A cofactor-assembly defect can mimic a defect in the glycine-cleavage enzymes themselves.","subject":{"id":"4d72b0cf-da5e-5f9e-9da8-0ee9082ec1a3","slug":"glrx5","display_name":"Human mitochondrial glutaredoxin 5 / GLRX5","entity_type_key":"protein"},"object":{"id":"0942d48b-22cc-5041-8e87-dc6349469bc3","slug":"lipoylation-disorder-glycine-accumulation","display_name":"Glycine accumulation in lipoylation disorders","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"b3342e73-d122-5558-b42f-068e48b6db15","stable_key":"5d8e27d8-6a74-5560-827f-3f90908bbc34:ala-glrx5-glycine-failure-event","event_type":"biochemical_relationship","label":"A cofactor-assembly defect can mimic a defect in the glycine-cleavage enzymes themselves.","description":"GLRX5-associated cases showed deficient protein lipoylation and glycine-cleavage activity with elevated glycine.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"206d41a9-3025-5cd2-8fa0-ccf9563d501a","slug":"glycine-cleavage-flux","display_name":"Glycine cleavage flux","entity_type_key":"cellular_process"},"role":"affected_process","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"78a93278-7e43-59c7-b097-31bbae21c771","slug":"gcsh","display_name":"Human glycine-cleavage H-protein / GCSH","entity_type_key":"protein"},"role":"cofactor_carrier","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":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"0942d48b-22cc-5041-8e87-dc6349469bc3","slug":"lipoylation-disorder-glycine-accumulation","display_name":"Glycine accumulation in lipoylation disorders","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/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":"A cofactor-assembly defect can mimic a defect in the glycine-cleavage enzymes themselves.","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. (2014). https://pubmed.ncbi.nlm.nih.gov/24334290/ DOI: 10.1093/brain/awt328","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Eight genetically explained patients within an eleven-person group","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":"c70c2bdb-0d36-56d6-8b03-12e8ed8ab9e1","evidence_kind":"source_excerpt","locator":"Lines 533-544","start_line":533,"end_line":544,"excerpt":"### ala-glrx5-glycine-failure\nGLRX5-associated cases showed deficient protein lipoylation and glycine-cleavage activity with elevated glycine.\nCondition category: machinery_impairment\nnutrient_topic: Alpha-lipoic acid research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A cofactor-assembly defect can mimic a defect in the glycine-cleavage enzymes themselves.\norganism: Human\ntissue_or_cell_type: Eight genetically explained patients within an eleven-person group\nexperimental_model: Variant nonketotic hyperglycinemia cohort and cell complementation\nlimitations: Phenotypes varied; respiratory-chain function was preserved in this series, unlike some other Fe-S disorders.\nexposure: LIAS, BOLA3 or GLRX5 variants; lipoate and mitochondrially targeted lipoate in cells\nevidence_span: {\"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\"}\n[ala-p24334290] Variant non ketotic hyperglycinemia is caused by mutations in LIAS, BOLA3 and the novel gene GLRX5. 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