Vitamin K and the Biosynthesis of Prothrombin

An NH2-terminal fragment produced by thrombin digestion of purified normal and of dicoumarol-induced prothrombin was isolated and characterized. These fragments which were found to have a molecular weight of approximately 27,000 had an identical amino acid and carbohydrate composition. The fragment from normal prothrombin binds Ca2+ while the corresponding fragment from the dicoumarol-induced prothrombin does not. Furthermore the fragment from normal prothrombin had Ca2+-dependent antigenic determinants but not the fragment from the dicoumarol-induced prothrombin. In addition a large COOH-terminal fragment was produced by thrombin digestion, which had identical electrophoretic and immunochemical properties from both prothrombins. In peptide maps prepared from thermolysin digests of the NH2-terminal fragments, untreated as well as reduced and aminoethylated, clear-cut differences were observed. These differences presumably reflect a postribosomal vitamin K-dependent modification of the normal prothrombin molecule.