{"id":"cc0a539b-f577-50cf-adf4-7f6f83843a35","stable_key":"dc8975b1-95ff-5d9b-be17-a1c04610cca7:mo-marc-tungsten","predicate":"abolishes_assayed_formation_of","statement":"Replacing molybdenum with tungsten during recombinant mARC1 production abolished NO formation.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"a9a23fa6-104f-55c6-926a-c81aaf27aa2c","mechanism_event_label":"A chemically similar metal could not replace molybdenum in this reaction.","subject":{"id":"46823cc9-76a9-5925-9ee9-f37ce916ad47","slug":"mtarc1-tungsten-substituted","display_name":"Tungsten-substituted recombinant human MTARC1","entity_type_key":"protein_state"},"object":{"id":"f2a6b7ab-ad41-5ada-8895-41d6ce42f4e4","slug":"nitric-oxide","display_name":"NO","entity_type_key":"small_molecule"},"evidence_count":1,"mechanism_event":{"id":"a9a23fa6-104f-55c6-926a-c81aaf27aa2c","stable_key":"dc8975b1-95ff-5d9b-be17-a1c04610cca7:mo-marc-tungsten-event","event_type":"biochemical_relationship","label":"A chemically similar metal could not replace molybdenum in this reaction.","description":"Replacing molybdenum with tungsten during recombinant mARC1 production abolished NO formation.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"9b22b727-d7d9-5731-a221-4aa8c7adcb4e","slug":"tungstate","display_name":"Tungstate / WO4(2-)","entity_type_key":"ion"},"role":"production exposure","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"36447b98-3392-559f-b76c-035726a2538e","slug":"molybdenum","display_name":"Molybdenum","entity_type_key":"nutrient_element"},"role":"normal metal","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""},{"entity":{"id":"46823cc9-76a9-5925-9ee9-f37ce916ad47","slug":"mtarc1-tungsten-substituted","display_name":"Tungsten-substituted recombinant human MTARC1","entity_type_key":"protein_state"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":2,"notes":""},{"entity":{"id":"f2a6b7ab-ad41-5ada-8895-41d6ce42f4e4","slug":"nitric-oxide","display_name":"NO","entity_type_key":"small_molecule"},"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/molybdenum-research/24500710.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"e4c2ab41c945d420266290d0241752039d7de2cb6223f9c64c7d0525c5688d9b\", \"start_char\": 0, \"end_char\": 1585, \"text_sha256\": \"e4c2ab41c945d420266290d0241752039d7de2cb6223f9c64c7d0525c5688d9b\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Recombinant human mARC1/mARC2, active-site mutation, tungsten replacement and HEK expression","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Reduced enzyme, nitrite, NADH/CYB5/CYB5R; pH 7.5 versus 6.5","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Shows nitrite-reducing capacity; its share of NO production in normal people and response to mineral intake are not established.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Molybdenum research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"molybdenum","display_name":"Molybdenum","entity_type_key":"nutrient_element"}},{"dimension":"organism","value_text":"Homo sapiens proteins and HEK cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"A chemically similar metal could not replace molybdenum in this reaction.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[mo-p24500710] Nitrite reductase and nitric-oxide synthase activity of the mitochondrial molybdopterin enzymes mARC1 and mARC2. (2014). https://pubmed.ncbi.nlm.nih.gov/24500710/ DOI: 10.1074/jbc.m114.555177","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Purified redox system and human cell model","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":"ab5d894c-857a-5526-bef9-f4b40d96ead7","evidence_kind":"source_excerpt","locator":"Lines 1080-1091","start_line":1080,"end_line":1091,"excerpt":"### mo-marc-tungsten\nReplacing molybdenum with tungsten during recombinant mARC1 production abolished NO formation.\nCondition category: machinery_impairment\nnutrient_topic: Molybdenum research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: A chemically similar metal could not replace molybdenum in this reaction.\norganism: Homo sapiens proteins and HEK cells\ntissue_or_cell_type: Purified redox system and human cell model\nexperimental_model: Recombinant human mARC1/mARC2, active-site mutation, tungsten replacement and HEK expression\nlimitations: Shows nitrite-reducing capacity; its share of NO production in normal people and response to mineral intake are not established.\nexposure: Reduced enzyme, nitrite, NADH/CYB5/CYB5R; pH 7.5 versus 6.5\nevidence_span: {\"source_cache\": \"artifacts/molybdenum-research/24500710.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"e4c2ab41c945d420266290d0241752039d7de2cb6223f9c64c7d0525c5688d9b\", \"start_char\": 0, \"end_char\": 1585, \"text_sha256\": \"e4c2ab41c945d420266290d0241752039d7de2cb6223f9c64c7d0525c5688d9b\"}\n[mo-p24500710] Nitrite reductase and nitric-oxide synthase activity of the mitochondrial molybdopterin enzymes mARC1 and mARC2. 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