Thrombin as a Proteolytic Enzyme

Abstract

Evidence is presented that thrombin hydrolyzes those synthetic substrates for proteolytic enzymes which contain arginine as the specific amino acid residue. These observations firmly establish the hydrolytic action of thrombin. The measurement of the hydrolytic activity of thrombin by TAMe (Toluenesulfonyl-1-arginine methyl ester) compares closely to measurements of its activity in the clotting of fibrinogen and suggests that the same enzyme center is involved in the action of thrombin on TAMe and on fibrinogen. Studies with synthetic substrates are consistent with the present concept of the enzymatic conversion of fibrinogen to an intermediate prior to the formation of the fibrin clot. Finally, it has been observed that TAMe inhibits the activation of prothrombin. While preliminary observations suggest that this inhibition is due to the formation of a complex between prothrombin and the synthetic substrate, other possible mechanisms for this inhibition are still under investigation.