{"id":"696b2303-2a8e-5179-8374-dc943984c5e2","stable_key":"4fef8d72-f107-5eb5-b2fb-483ca85465e0:k2-ubiad1-warfarin","predicate":"did_not_inhibit","statement":"Warfarin did not inhibit UBIAD1-mediated MK-4 biosynthesis in the reported experiments.","claim_class":"mechanistic","status":"source_derived_draft","evidence_grade":"ungraded","direction":"context_dependent","is_public":true,"mechanism_event_id":"9a161960-2b69-5eb6-b19e-770b08e4abc7","mechanism_event_label":"The drug blocks vitamin K recycling, but that is a different enzyme step from making MK-4.","subject":{"id":"ee94b256-deeb-5795-8b6e-6e388576d464","slug":"warfarin","display_name":"Warfarin","entity_type_key":"small_molecule"},"object":{"id":"c06c54bb-69ce-58a3-a904-0647dbaf3577","slug":"mk4-biosynthesis","display_name":"Menaquinone-4 biosynthesis","entity_type_key":"cellular_process"},"evidence_count":1,"mechanism_event":{"id":"9a161960-2b69-5eb6-b19e-770b08e4abc7","stable_key":"4fef8d72-f107-5eb5-b2fb-483ca85465e0:k2-ubiad1-warfarin-event","event_type":"biochemical_relationship","label":"The drug blocks vitamin K recycling, but that is a different enzyme step from making MK-4.","description":"Warfarin did not inhibit UBIAD1-mediated MK-4 biosynthesis in the reported experiments.","status":"provisional","compartment":null,"participants":[{"entity":{"id":"ee94b256-deeb-5795-8b6e-6e388576d464","slug":"warfarin","display_name":"Warfarin","entity_type_key":"small_molecule"},"role":"subject","stoichiometry":null,"state_label":"","sequence_order":0,"notes":""},{"entity":{"id":"c06c54bb-69ce-58a3-a904-0647dbaf3577","slug":"mk4-biosynthesis","display_name":"Menaquinone-4 biosynthesis","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/20953171.abstract.txt\", \"locator\": \"Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets\", \"file_sha256\": \"b8786e664d3b32db7b0cca72c710e24f1546e14f0a69c031908400731174cea3\", \"start_char\": 0, \"end_char\": 2006, \"text_sha256\": \"b8786e664d3b32db7b0cca72c710e24f1546e14f0a69c031908400731174cea3\"}","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"experimental_model","value_text":"Gene knockdown, heterologous expression, isotope conversion and NMR","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"exposure","value_text":"Labeled vitamin K precursors, UBIAD1 knockdown and expression","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"limitations","value_text":"Identifies a biosynthetic enzyme, not a clinical requirement to supplement MK-4. K1-derived MK-4 synthesis does not make humans independent of external vitamin K precursors.","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 UBIAD1 in human and insect-cell systems; mouse localization","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"plain_language","value_text":"The drug blocks vitamin K recycling, but that is a different enzyme step from making MK-4.","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"primary_references","value_text":"[k2-p20953171] Identification of UBIAD1 as a novel human menaquinone-4 biosynthetic enzyme. (2010). https://pubmed.ncbi.nlm.nih.gov/20953171/ DOI: 10.1038/nature09464","comparator":null,"unit":null,"notes":"","entity":null},{"dimension":"tissue_or_cell_type","value_text":"MK-4 synthesis","comparator":null,"unit":null,"notes":"","entity":null}],"evidence":[{"id":"0662c042-49dd-5f1f-9495-72d570236505","evidence_kind":"source_excerpt","locator":"Lines 162-173","start_line":162,"end_line":173,"excerpt":"### k2-ubiad1-warfarin\nWarfarin did not inhibit UBIAD1-mediated MK-4 biosynthesis in the reported experiments.\nCondition category: normal\nnutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect.\nplain_language: The drug blocks vitamin K recycling, but that is a different enzyme step from making MK-4.\norganism: Human UBIAD1 in human and insect-cell systems; mouse localization\ntissue_or_cell_type: MK-4 synthesis\nexperimental_model: Gene knockdown, heterologous expression, isotope conversion and NMR\nlimitations: Identifies a biosynthetic enzyme, not a clinical requirement to supplement MK-4. 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