Changes in phylloquinone epoxidase activity related to prothrombin synthesis and microsomal clotting activity in the rat.
The oxidation of phylloquinone to the 2,3-epoxide (by phylloquinone epoxidase) was studied in liver from control and warfarin-resistant rats. The reaction requires microsomal fraction, soluble protein, a heat-stable soluble factor and O(2). It is not inhibited by CO or CN(-). Epoxidase activity was stimulated if plasma prothrombin was lowered either by anticoagulants or the absence of vitamin K. The activity of the enzyme rapidly returned to normal values after the administration of vitamin K to hypoprothrombinaemic rats. These differences in the activity of the enzyme occur in the microsomal fraction and not the cytosol. A thrombin-generating polypeptide that accumulates in microsomal fraction of hypothrombinaemic rats correlated directly with epoxidase activity. These data support the view that enzymic interconversion of phylloquinone and its 2,3-epoxide participates in the biological activity of vitamin K.
D000818:Animals; D000925:Anticoagulants; D001777:Blood Coagulation; D002248:Carbon Monoxide / Q000494:pharmacology; D003486:Cyanides / Q000494:pharmacology; D004351:Drug Resistance; D004492:Edetic Acid / Q000494:pharmacology; D004852:Epoxy Compounds; D005260:Female; D005182:Flavin-Adenine Dinucleotide / Q000494:pharmacology; D007020:Hypoprothrombinemias / Q000188:drug therapy; D007700:Kinetics; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009243:NAD / Q000494:pharmacology; D009249:NADP / Q000494:pharmacology; D010088:Oxidoreductases / Q000378:metabolism*; D010105:Oxygenases; D011506:Proteins; D011516:Prothrombin / Q000096:biosynthesis*; D051381:Rats; D014812:Vitamin K / Q000494:pharmacology*; D010837:Vitamin K 1 / Q000378:metabolism*; D014813:Vitamin K Deficiency / Q000378:metabolism; D014859:Warfarin
D000925:Anticoagulants; D003486:Cyanides; D004852:Epoxy Compounds; D011506:Proteins; D009243:NAD; D014812:Vitamin K; D005182:Flavin-Adenine Dinucleotide; D009249:NADP; D014859:Warfarin; D002248:Carbon Monoxide; D010837:Vitamin K 1; D011516:Prothrombin; D004492:Edetic Acid; D010088:Oxidoreductases; D010105:Oxygenases; C022396:phylloquinone monooxygenase (2,3-epoxidizing)