Publisher Summary This chapter describes the metabolism and properties of a liver precursor to prothrombin. The production of the K-dependent clotting factors could be experimentally regulated and studied in a number of laboratory species. Vitamin K could theoretically function at a number of sites in the chain of metabolic events that lead from the production of an mRNA molecule specific for the polypeptide chain of prothrombin within the nucleus of the hepatocyte to the secretion of a completed prothrombin molecule into the plasma. A number of cell-free systems that produce factor VII upon incubation have also been described. The direct evidence of the presence of a precursor has been obtained by the demonstration that the prothrombin produced when hypoprothrombinemic rats are given vitamin K does not contain radioactive amino acids if they are administered at the same time as the vitamin. The precursor does not adsorb to insoluble barium salts, and although it is inactive in the standard two-stage assay for prothrombin, it can be degraded by thrombin in the same manner as prothrombin to yield a 55,000 DA basic fragment that contains the thrombin portion of the protein and a 25,000 molecular weight fragment.