{"id":"a1deb71c-180e-5d6d-a342-dbbb6fb7a71d","stable_key":"e13b03e1-a614-543a-ac1b-97df18cfe30d:iron-glrx5-fech","predicate":"impairment_reduced","statement":"Ferrochelatase protein abundance increased in patient-derived cells, while its catalytic activity was drastically reduced.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"bfd31661-5c8a-5c3d-9091-625134661e6d","mechanism_event_label":"More enzyme protein did not mean more working enzyme.","subject":{"id":"4d72b0cf-da5e-5f9e-9da8-0ee9082ec1a3","slug":"glrx5","display_name":"Human mitochondrial glutaredoxin 5 / GLRX5","entity_type_key":"protein"},"object":{"id":"2a79ab84-aa67-55cc-a04a-0dec072bdf60","slug":"ferrochelatase-activity","display_name":"Ferrochelatase catalytic activity","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"bfd31661-5c8a-5c3d-9091-625134661e6d","stable_key":"e13b03e1-a614-543a-ac1b-97df18cfe30d:iron-glrx5-fech-event","event_type":"biochemical_relationship","label":"More enzyme protein did not mean more working enzyme.","description":"Ferrochelatase protein abundance increased in patient-derived cells, while its catalytic activity was drastically reduced.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"b62a3c7f-ddf3-59e8-86c8-6d00c041aa21","slug":"fech","display_name":"Human ferrochelatase / FECH","entity_type_key":"protein"},"role":"affected_enzyme","stoichiometry":null,"state_label":"","sequence_order":0,"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":1,"notes":""},{"entity":{"id":"2a79ab84-aa67-55cc-a04a-0dec072bdf60","slug":"ferrochelatase-activity","display_name":"Ferrochelatase catalytic activity","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":2,"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/iron-research/30660387.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"ea84d16e2c32450b285c269acb4a5343a8af27b49d8d1827afd3ad1961b8a61e\", \"start_char\": 0, \"end_char\": 1625, \"text_sha256\": \"ea84d16e2c32450b285c269acb4a5343a8af27b49d8d1827afd3ad1961b8a61e\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Patient-derived cell biochemistry and variant structural analysis","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Compound-heterozygous GLRX5 variants","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"One patient; reduced succinyl-CoA contribution to ALAS2 dysfunction was proposed, not definitively isolated.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Iron research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"iron","display_name":"Iron","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Human GLRX5-deficient patient","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"More enzyme protein did not mean more working enzyme.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[iron-p30660387] GLRX5 mutations impair heme biosynthetic enzymes ALA synthase 2 and ferrochelatase in Human congenital sideroblastic anemia. (2019). https://pubmed.ncbi.nlm.nih.gov/30660387/ DOI: 10.1016/j.ymgme.2018.12.012","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Lymphoblastoid and CD34-positive 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":"dca39b8f-16fc-5fa2-9ade-b13ac1456cd5","evidence_kind":"source_excerpt","locator":"Lines 1070-1081","start_line":1070,"end_line":1081,"excerpt":"### iron-glrx5-fech\nFerrochelatase protein abundance increased in patient-derived cells, while its catalytic activity was drastically reduced.\nCondition category: machinery_impairment\nnutrient_topic: Iron research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: More enzyme protein did not mean more working enzyme.\norganism: Human GLRX5-deficient patient\ntissue_or_cell_type: Lymphoblastoid and CD34-positive cells\nexperimental_model: Patient-derived cell biochemistry and variant structural analysis\nlimitations: One patient; reduced succinyl-CoA contribution to ALAS2 dysfunction was proposed, not definitively isolated.\nexposure: Compound-heterozygous GLRX5 variants\nevidence_span: {\"source_cache\": \"artifacts/iron-research/30660387.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"ea84d16e2c32450b285c269acb4a5343a8af27b49d8d1827afd3ad1961b8a61e\", \"start_char\": 0, \"end_char\": 1625, \"text_sha256\": \"ea84d16e2c32450b285c269acb4a5343a8af27b49d8d1827afd3ad1961b8a61e\"}\n[iron-p30660387] GLRX5 mutations impair heme biosynthetic enzymes ALA synthase 2 and ferrochelatase in Human congenital sideroblastic anemia. 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