The Role of Vitamin K in Clotting Factor Biosynthesis

An acquired vitamin K deficiency produced by anticoagulant administration results in the secretion into the plasma of large quantities of uncarboxylated and partially carboxylated forms of vitamin K-dependent clotting factors in both the human and bovine. The genes for the vitamin K-dependent proteins have been characterized by DNA sequence analysis, and the similarities of their structures have been reviewed. Three of the classical vitamin K-dependent clotting factors, factors VII, IX, and X, were first discovered because of a congenital abnormality that resulted in a coagulation disorder. The availability of the well-characterized cellular expression systems has been utilized to test the hypothesis that the homologous amino terminal propeptide of the vitamin K-dependent proteins is an important signal for γ-carboxylation. The importance of specific regions or residues of the propeptide for carboxylase recognition has also been assessed through the synthesis of peptide substrates for the carboxylase.