Vitamin K activity and metabolism of vitamin K-1 epoxide-1,4-diol. 1982

R G Bell

Vitamin K-1 epoxide, the major metabolite of vitamin k-1, has similar activity to vitamin K-1 in inducing prothrombin synthesis and protein carboxylation. The high activity of K-1 epoxide could be due to its conversion to vitamin K-1 hydroquinone without going through vitamin K-1. A logical intermediate in this conversion would be vitamin K-1 epoxide-1,4-diol. The epoxide diol was synthesized and clearly stimulated prothrombin synthesis in vitamin K deficient rats at a minimum dose of 100 micrograms/kg body weight. Since vitamin K-1 produced a similar response at a minimum dose of 1 microgram/kg, the epoxide diol had about 1% of the activity of vitamin K-1. [3H]K-1 or [3H]epoxide could not be detected as metabolites of [3H]epoxide diol indicating that the activity of epoxide diol was probably not due to its conversion to K-1 hydroquinone, since any [3H]hydroquinone formed would be oxidized in air to [3H]K-1 during analysis. Vitamin K-1 epoxide diol represents a new type of structure possessing vitamin K activity. It is probably not active itself but has to be converted to an active compound since there is a delay in the response to the diol and the activity is completely blocked by Warfarin.

UI MeSH Term Description Entries
D010837 Vitamin K 1 A family of phylloquinones that contains a ring of 2-methyl-1,4-naphthoquinone and an isoprenoid side chain. Members of this group of vitamin K 1 have only one double bond on the proximal isoprene unit. Rich sources of vitamin K 1 include green plants, algae, and photosynthetic bacteria. Vitamin K1 has antihemorrhagic and prothrombogenic activity. Phylloquinone,Phytomenadione,Phytonadione,Aquamephyton,Konakion,Phyllohydroquinone,Vitamin K1
D011516 Prothrombin A plasma protein that is the inactive precursor of thrombin. It is converted to thrombin by a prothrombin activator complex consisting of factor Xa, factor V, phospholipid, and calcium ions. Deficiency of prothrombin leads to hypoprothrombinemia. Coagulation Factor II,Factor II,Blood Coagulation Factor II,Differentiation Reversal Factor,Factor II, Coagulation,Factor, Differentiation Reversal,II, Coagulation Factor
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia
D014812 Vitamin K A lipid cofactor that is required for normal blood clotting. Several forms of vitamin K have been identified: VITAMIN K 1 (phytomenadione) derived from plants, VITAMIN K 2 (menaquinone) from bacteria, and synthetic naphthoquinone provitamins, VITAMIN K 3 (menadione). Vitamin K 3 provitamins, after being alkylated in vivo, exhibit the antifibrinolytic activity of vitamin K. Green leafy vegetables, liver, cheese, butter, and egg yolk are good sources of vitamin K.
D014813 Vitamin K Deficiency A nutritional condition produced by a deficiency of VITAMIN K in the diet, characterized by an increased tendency to hemorrhage (HEMORRHAGIC DISORDERS). Such bleeding episodes may be particularly severe in newborn infants. (From Cecil Textbook of Medicine, 19th ed, p1182) Deficiency, Vitamin K,Deficiencies, Vitamin K,Vitamin K Deficiencies
D014859 Warfarin An anticoagulant that acts by inhibiting the synthesis of vitamin K-dependent coagulation factors. Warfarin is indicated for the prophylaxis and/or treatment of venous thrombosis and its extension, pulmonary embolism, and atrial fibrillation with embolization. It is also used as an adjunct in the prophylaxis of systemic embolism after myocardial infarction. Warfarin is also used as a rodenticide. 4-Hydroxy-3-(3-oxo-1-phenylbutyl)-2H-1-benzopyran-2-one,Aldocumar,Apo-Warfarin,Coumadin,Coumadine,Gen-Warfarin,Marevan,Tedicumar,Warfant,Warfarin Potassium,Warfarin Sodium,Potassium, Warfarin,Sodium, Warfarin
D051381 Rats The common name for the genus Rattus. Rattus,Rats, Laboratory,Rats, Norway,Rattus norvegicus,Laboratory Rat,Laboratory Rats,Norway Rat,Norway Rats,Rat,Rat, Laboratory,Rat, Norway,norvegicus, Rattus

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