Activation of Prothrombin

¹ From the Department of Physiology and Pharmacology, Wayne State University College of Medicine, Detroit, Michigan

In experiments with purified biothrombin, it was found that strong solutions of sodium citrate or protamine sulfate (0.1% w/v) or purified platelet factor 3 depress the esterase activity and leave the clotting power unaltered. Apparently a depression of esterase activity is beneficial for the autocatalytic activation of purified prothrombin. In protamine sulfate solution, prothrombin gradually becomes thrombin and the yield of thrombin is even higher than in 25% sodium citrate solution. Prothrombin also depresses the esterase activity of biothrombin, and itself serves as a substrate for the enzyme thrombin. When prothrombin becomes an inactive derivative or a substance refractory to being converted to thrombin in the presence of Ac-globulin, thromboplastin and calcium ions, it can nevertheless be changed to thrombin with the use of thrombin as a catalyst, just as was previously accomplished with the use of 25% sodium citrate solutions. Theoretically, a prothrombin derivative(s) can serve as substrate competitor for thrombin and thus be an accelerator of prothrombin activation, or the derivative, under appropriate conditions can itself give rise to thrombin. Thrombin as activator of prothrombin can account for all observed conditions of prothrombin activation. The discovery of thrombin as activator of prothrombin offers a simplified view of the entire blood coagulation mechanisms. Two equations can describe the basic events: Prothrombin(See PDF for Equation)Thrombin; Fibrinogen(See PDF for Equation)Fibrin. Other factors support the production and enzymic function of thrombin and these are called procoagulants. Opposed to these, and normally in exact balance, are those factors that hinder the production or function of thrombin and these are called anticoagulants. In the presence of thrombin prothrombin can change to thrombin without Ac-globulin. Plasma Ac-globulin changes to serum Ac-globulin in the presence of thrombin but not with esterase thrombin. Consequently, the depression of esterase activity does not impair the capacity of thrombin to make the beneficial alteration in Ac-globulin.