The Conversion of Prothrombin to Thrombin

Abstract

Complete activation of prothrombin (mol wt 72,000 to 74,000) by activated Factor X, Factor V, and phospholipid results in the formation of thrombin (mol wt 37,000) and two activation fragments (Fragment 1 and Fragment 2) which cannot be activated to thrombin. Partial activation of prothrombin with activated Factor X allows the isolation of two products which can be further activated to thrombin. These products are designated Intermediate 1 and Intermediate 2. Incubation of prothrombin with thrombin results in the formation of Intermediate 1 (mol wt 48,000 to 50,000) and Fragment 1 (mol wt 22,000 to 24,000). Intermediate 1 activation requires two proteolytic cleavages. The first cleavage of Intermediate 1 by activated Factor X results in the formation of Intermediate 2 (mol wt 37,000 to 38,000) and Fragment 2 (mol wt 12,800). The second cleavage by activated Factor X forms the A and B chains of thrombin. The two activation fragments generated in the presence of activated Factor X alone are indistinguishable from those generated in the presence of activated Factor X, Factor V, and phospholipid by the criteria of disc gel electrophoresis, sodium dodecyl sulfate gel electrophoresis, ion exchange chromatography, and amino acid composition.