Inhibition by warfarin of prothrombin synthesis and of lipid-saccharide synthesis in rat liver.
In vivo and in vitro studies using [3H]glucosamine incorporation into prothrombin and into glycolipids were conducted in rat liver to determine the role of lipid-saccharides in the biosynthesis of prothrombin. In vivo studies demonstrated that 10 mg warfarin/kg inhibited the incorporation of radiolabeled glucosamine into liver prothrombin and glycolipids. This inhibition was similar to the kinetics of inhibition of prothrombin synthesis in the liver. In vitro studies demonstrated a time-dependent increase in the incorporation of radiolabeled glucosamine into lipid-saccharides and prothrombin. This incorporation was inhibited 50% by 5 . 10(-4) M warfarin. Warfarin also inhibited the incorporation of radiolabeled glucosamine into glycolipids in a dose-related manner. In all studies, vitamin K-1 reversed the inhibition of glucosamine incorporation into glycolipids and into prothrombin.
D000818:Animals; D003864:Depression, Chemical; D005944:Glucosamine / Q000378:metabolism; D006017:Glycolipids / Q000096:biosynthesis*; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D009005:Monosaccharides / Q000378:metabolism; D009844:Oligosaccharides / Q000378:metabolism; D011516:Prothrombin / Q000096:biosynthesis*; D051381:Rats; D010837:Vitamin K 1 / Q000494:pharmacology; D014859:Warfarin / Q000494:pharmacology*
D006017:Glycolipids; D009005:Monosaccharides; D009844:Oligosaccharides; D014859:Warfarin; D010837:Vitamin K 1; D011516:Prothrombin; D005944:Glucosamine