{"id":"96955c95-904f-5f4d-98f8-1f3193431a4c","stable_key":"be889add-cec8-500b-be89-676431432a70:mn-enz-sod2-iron-peroxidase","predicate":"catalyzes","statement":"Iron incorporation into SOD2 generated a form that used hydrogen peroxide for prooxidant peroxidase chemistry in the reported biochemical and cell experiments.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"positive","is_public":true,"mechanism_event_id":"e90f5664-7fda-56d5-b5fc-4b377ae85a8d","mechanism_event_label":"Iron in the SOD2 site can change what the enzyme does.","subject":{"id":"269c0999-9f0e-5c8d-9839-4c402ac2467d","slug":"sod2-iron-loaded","display_name":"Iron-loaded human SOD2","entity_type_key":"protein_state"},"object":{"id":"1d4ace29-0ec9-5deb-bd55-4116032fe7a4","slug":"sod2-peroxidase-activity","display_name":"Iron-loaded SOD2 peroxidase activity","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"e90f5664-7fda-56d5-b5fc-4b377ae85a8d","stable_key":"be889add-cec8-500b-be89-676431432a70:mn-enz-sod2-iron-peroxidase-event","event_type":"biochemical_relationship","label":"Iron in the SOD2 site can change what the enzyme does.","description":"Iron incorporation into SOD2 generated a form that used hydrogen peroxide for prooxidant peroxidase chemistry in the reported biochemical and cell experiments.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"269c0999-9f0e-5c8d-9839-4c402ac2467d","slug":"sod2-iron-loaded","display_name":"Iron-loaded human SOD2","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"1d4ace29-0ec9-5deb-bd55-4116032fe7a4","slug":"sod2-peroxidase-activity","display_name":"Iron-loaded SOD2 peroxidase activity","entity_type_key":"cellular_process"},"role":"object","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"89bcaf42-b4ab-5760-8c2e-44eace10cee0","slug":"iron","display_name":"Iron","entity_type_key":"nutrient_element"},"role":"competing metal identity","stoichiometry":null,"state_label":"","sequence_order":2,"notes":"Element identity only; no fixed oxidation state assigned to total tissue iron or iron throughout the enzyme redox reaction."},{"entity":{"id":"a8082b11-c484-5792-bb81-48e8e699cbe4","slug":"manganese-ion","display_name":"Mn2+","entity_type_key":"ion"},"role":"normal cofactor","stoichiometry":null,"state_label":"","sequence_order":3,"notes":""},{"entity":{"id":"da9d64bc-69d4-5d97-90a4-8f0ed03e0ac8","slug":"hydrogen-peroxide","display_name":"Hydrogen peroxide","entity_type_key":"small_molecule"},"role":"substrate","stoichiometry":null,"state_label":"","sequence_order":4,"notes":""}]},"contexts":[{"dimension":"cross_nutrient","value_text":"Iron misincorporation competes with normal Mn cofactor chemistry; iron-loaded SOD2 is not functional replacement.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Purified SOD2, SOD2-overexpressing human cells, and dietary C57BL/6J mouse experiments","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Enzyme metal substitution; low Mn:Fe cell media; altered mouse diets","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Iron-loading experiments and overexpression cell models; no human prevalence or dietary threshold inferred.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Manganese research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"manganese","display_name":"Manganese","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Homo sapiens; Mus musculus","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Iron in the SOD2 site can change what the enzyme does.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[mn-enz-29398562] Switch of Mitochondrial Superoxide Dismutase into a Prooxidant Peroxidase in Manganese-Deficient Cells and Mice. (2018). https://pubmed.ncbi.nlm.nih.gov/29398562/ DOI: 10.1016/j.chembiol.2018.01.007","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified enzyme, cultured cells and mouse liver","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"838c821f-b99b-5f5e-9c8d-cb3190d279c8","evidence_kind":"source_excerpt","locator":"Lines 495-506","start_line":495,"end_line":506,"excerpt":"### mn-enz-sod2-iron-peroxidase\nIron incorporation into SOD2 generated a form that used hydrogen peroxide for prooxidant peroxidase chemistry in the reported biochemical and cell experiments.\nCondition category: normal\nnutrient_topic: Manganese research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Iron in the SOD2 site can change what the enzyme does.\norganism: Homo sapiens; Mus musculus\ntissue_or_cell_type: Purified enzyme, cultured cells and mouse liver\nexperimental_model: Purified SOD2, SOD2-overexpressing human cells, and dietary C57BL/6J mouse experiments\nlimitations: Iron-loading experiments and overexpression cell models; no human prevalence or dietary threshold inferred.\nexposure: Enzyme metal substitution; low Mn:Fe cell media; altered mouse diets\ncross_nutrient: Iron misincorporation competes with normal Mn cofactor chemistry; iron-loaded SOD2 is not functional replacement.\n[mn-enz-29398562] Switch of Mitochondrial Superoxide Dismutase into a Prooxidant Peroxidase in Manganese-Deficient Cells and Mice. 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