{"id":"7533a4dc-ec97-5a83-b8a1-d46c1d6702c4","stable_key":"4fef8d72-f107-5eb5-b2fb-483ca85465e0:k2-dhodh-not-k-reductase","predicate":"did_not_support","statement":"DHODH did not support vitamin K-dependent carboxylation in the tested reporter system despite its separate ubiquinone-associated ferroptosis role.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"bf80a614-1f24-5084-8aeb-824070c91c31","mechanism_event_label":"Similar antioxidant roles do not make two enzymes interchangeable.","subject":{"id":"34f8e936-32ed-55ed-b0a6-8b26330abea5","slug":"dhodh","display_name":"Human dihydroorotate dehydrogenase / DHODH","entity_type_key":"protein"},"object":{"id":"de0220e7-19ea-5b7e-8521-57abbfe8e945","slug":"vitamin-k-dependent-carboxylation","display_name":"Vitamin K-dependent protein gamma-carboxylation","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"bf80a614-1f24-5084-8aeb-824070c91c31","stable_key":"4fef8d72-f107-5eb5-b2fb-483ca85465e0:k2-dhodh-not-k-reductase-event","event_type":"biochemical_relationship","label":"Similar antioxidant roles do not make two enzymes interchangeable.","description":"DHODH did not support vitamin K-dependent carboxylation in the tested reporter system despite its separate ubiquinone-associated ferroptosis role.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"34f8e936-32ed-55ed-b0a6-8b26330abea5","slug":"dhodh","display_name":"Human dihydroorotate dehydrogenase / DHODH","entity_type_key":"protein"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"de0220e7-19ea-5b7e-8521-57abbfe8e945","slug":"vitamin-k-dependent-carboxylation","display_name":"Vitamin K-dependent protein gamma-carboxylation","entity_type_key":"cellular_process"},"role":"target","stoichiometry":null,"state_label":"","sequence_order":1,"notes":""}]},"contexts":[{"dimension":"evidence_span","value_text":"{\"source_cache\": \"artifacts/k2-research/36788244.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"5fda09197d386351a1b1d261c9b385db36e02eab0c238bf18599d7086b501f93\", \"start_char\": 0, \"end_char\": 1359, \"text_sha256\": \"5fda09197d386351a1b1d261c9b385db36e02eab0c238bf18599d7086b501f93\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Genome-wide CRISPR screen and reporter biochemistry","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"FSP1 knockout/inhibition and DHODH comparison","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Supports cycle biochemistry; a different ferroptosis defense enzyme need not share the same vitamin K function.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"nutrient_topic","value_text":"Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect.","comparator":null,"unit":null,"notes":"","entity":{"slug":"k2","display_name":"Vitamin K2 / menaquinone family","entity_type_key":"chemical_species"}},{"dimension":"organism","value_text":"Human vitamin K-dependent reporter cells","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"Similar antioxidant roles do not make two enzymes interchangeable.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[k2-p36788244] A genome-wide CRISPR-Cas9 knockout screen identifies FSP1 as the warfarin-resistant vitamin K reductase. (2023). https://pubmed.ncbi.nlm.nih.gov/36788244/ DOI: 10.1038/s41467-023-36446-8","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"Warfarin-resistant quinone reduction","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"688b3988-699f-5b69-93e7-d2614139e90e","evidence_kind":"source_excerpt","locator":"Lines 838-849","start_line":838,"end_line":849,"excerpt":"### k2-dhodh-not-k-reductase\nDHODH did not support vitamin K-dependent carboxylation in the tested reporter system despite its separate ubiquinone-associated ferroptosis role.\nCondition category: normal\nnutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: Similar antioxidant roles do not make two enzymes interchangeable.\norganism: Human vitamin K-dependent reporter cells\ntissue_or_cell_type: Warfarin-resistant quinone reduction\nexperimental_model: Genome-wide CRISPR screen and reporter biochemistry\nlimitations: Supports cycle biochemistry; a different ferroptosis defense enzyme need not share the same vitamin K function.\nexposure: FSP1 knockout/inhibition and DHODH comparison\nevidence_span: {\"source_cache\": \"artifacts/k2-research/36788244.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"5fda09197d386351a1b1d261c9b385db36e02eab0c238bf18599d7086b501f93\", \"start_char\": 0, \"end_char\": 1359, \"text_sha256\": \"5fda09197d386351a1b1d261c9b385db36e02eab0c238bf18599d7086b501f93\"}\n[k2-p36788244] A genome-wide CRISPR-Cas9 knockout screen identifies FSP1 as the warfarin-resistant vitamin K reductase. (2023). https://pubmed.ncbi.nlm.nih.gov/36788244/ DOI: 10.1038/s41467-023-36446-8","model_system":"Genome-wide CRISPR screen and reporter biochemistry","directness":"author_interpretation","verification_status":"source_derived_draft","notes":"Exact curation-document quotation, not publisher quotation. Study references: [k2-p36788244] A genome-wide CRISPR-Cas9 knockout screen identifies FSP1 as the warfarin-resistant vitamin K reductase. (2023). https://pubmed.ncbi.nlm.nih.gov/36788244/ DOI: 10.1038/s41467-023-36446-8","relationship":"supports","weight":1.0,"link_notes":"","source":{"id":"dfeae572-af3d-5042-a10e-e67596f9ab28","stable_key":"import-4fef8d72-f107-5eb5-b2fb-483ca85465e0","title":"Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17)","document_type":"imported_text","citation_label":"AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text.","file_path":"","sha256":"dc31aff21110d09b025c177e03b4c5ca8349d52bf5f962285fdbfcf660c0e4f6","revision_id":"850887db-34f6-55aa-9d3e-b8fd3a4a5de3","review_status":"unverified_draft","notes":""}}],"relations":[],"conflicts":[],"corrections":[],"research":null}