Acquired vitamin K-dependent carboxylation deficiency in liver disease.
gamma-Carboxyglutamic acid residues on prothrombin are synthesized from glutamic acid on a prothrombin precursor in the liver through a vitamin K-dependent carboxylase. In the absence of vitamin K or in the presence of vitamin K antagonists, an inert form of prothrombin - abnormal prothrombin - circulates in the blood. We have developed specific immunoassays for native and abnormal human prothrombin. The prothrombin concentration in our normal subjects was 108 +/- 19 microgram per milliliter. The abnormal-prothrombin concentration varied over four orders of magnitude between the limits of detection in normal plasma and the level in patients with cirrhosis (0 to 5 microgram per milliliter), acute hepatitis (0 to 33 microgram per milliliter), or vitamin K deficiency (32 to 100 microgram per milliliter) and in those treated with sodium warfarin (12 to 65 microgram per milliliter). These studies indicate that abnormal prothrombin is not a component of normal plasma but appears in a variety of hepatic and nutritional disorders characterized by impaired hepatic vitamin-K-dependent carboxylation.
D000328:Adult; D000368:Aged; D019735:Carbon-Carbon Ligases; D000939:Epitopes; D005260:Female; D006505:Hepatitis / Q000201:enzymology; D006801:Humans; D008025:Ligases / Q000172:deficiency*; D008099:Liver / Q000201:enzymology; D008103:Liver Cirrhosis / Q000201:enzymology; D008107:Liver Diseases / Q000097:blood / Q000201:enzymology*; D008297:Male; D008875:Middle Aged; D011516:Prothrombin / Q000096:biosynthesis* / Q000276:immunology / Q000302:isolation & purification; D011517:Prothrombin Time; D014813:Vitamin K Deficiency / Q000201:enzymology; D014859:Warfarin / Q000009:adverse effects
D000939:Epitopes; D014859:Warfarin; D011516:Prothrombin; D008025:Ligases; D019735:Carbon-Carbon Ligases; C020660:glutamyl carboxylase