Proteolytic and polymerase activity of thrombin

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

In addition to splitting peptides from fibrinogen, thrombin is necessary for the polymerization of fibrin monomer. Thrombin also uses fibrin as a substrate and eventually the clot may lyse. On the basis of these views, previous equations used to outline the events when thrombin and fibrinogen are mixed can be revised as follows: Proteolysis: F + T f + P + T (1) Polymerization: Nf + T NfT (2) (fibrin clot) Proteolysis: NfT Inf + T + P₂ (3) F is fibrinogen, T is thrombin, f is fibrin monomer, P is peptides and carbohydrates, N is any number, Inf is inactive fibrin monomer, and P₂ is peptides or any reaction products. As the thrombin concentration increases the polymerization time becomes shorter. TAMe retards the polymerization time. For a given thrombin concentration the clotting time of fibrinogen may be inversely proportional to the concentration of fibrinogen. Most of the clotting time is accounted for as polymerization time, but the amount of thrombin required for the latter is relatively small. In 3 m urea solution thrombin may irreversibly lose its activity. When protected by a substrate such as TAMe, fibrinogen or fibrin, thrombin is active in urea solution. The activity then depends upon TAMe concentration under conditions when the enzyme behaves as if saturated with the substrate. To have this activity in urea solution the substrate must be in the urea before the thrombin is added. Esterase thrombin also uses fibrin as a substrate; it is, however, not a polymerase. It does not use fibrinogen as a substrate.