ABSTRACT
A general understanding of the properties of the vitamin K-dependent carboxylase was gained from studies utilizing the crude detergent-solubilized microsomal preparation as a source of enzyme activity, and small Glu-containing peptides as substrates. The critical vitamin K-dependent difference in the properties of the active and “abnormal” form of prothrombin was eventually shown to be the inability of the abnormal protein to participate in the calcium-dependent phospholipid-stimulated activation of prothrombin by factor X. The vitamin K-dependent proteins contain multiple Gla residues, and mature proteins from vitamin K-replete animals are carboxylated at all of the potential Gla sites. Gla residues which are one of the end products of the intracellular degradation of vitamin K-dependent proteins are not further metabolized, but are excreted in the urine. In the adult human the extent of Gla excretion is in the range of 50 µmol/day, indicating that a similar amount must be formed each day to maintain a steady-state cellular concentration of vitamin K-dependent proteins.
