Fibrinogen-fibrin conversion Step 3: Clotting

FIGURE 15.5 The cascade of activation steps leading to blood clotting. The intrinsic and extrinsic pathways converge at Factor X, and the final common pathway involves the activation of thrombin and its conversion of fibrinogen into fibrin, which aggregates into ordered filamentous arrays that become cross-linked to form the clot. 

The best-characterized part of the clotting process is the final step in the cascade the conversion of fibrinogen into fibrin by thrombin, a proteolytic enzyme. Fibrinogen is made up of three globular units connected by two... 

Thrombin attacks synthetic esters, namely tosyl l-arginine methyl ester (TAMe), and when thrombin is treated with DIPT, the loss of esterase activity is proportional to the loss of clotting activity. Studies with synthetic esters have suggested that, as with trypsin, the reaction between thrombin and its substrates occurs in three steps an enzyme-substrate complex is formed the acyl portion of the ester is transferred to the enzyme, which becomes acylated while the alcoholic portion of the ester is released and the enzyme is deacylated and the peptide is transferred to water. The natural substrate of thrombin is fibrinogen. In addition to converting fibrinogen to fibrin, thrombin releases the contractile protein from platelets, activates fibrinase, and may participate in the conversion of prothrombin to thrombin. 

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