Enzymes thrombin

The proteolytic enzyme thrombin is known to play a ciucial role in the overall thrombotic event leading to... 

Fig. 6.12. Two-step activation of a poly(vinyl alcohol)-linker-gentamycin device for wound-selective delivery of the antibiotic [44]. The overexpressed enzyme thrombin is the activity targeted by the thrombin-sensitive peptide linker.

The ability of blood to clot is so important that there are two separate pathways that converge to ensure sufficient activation of the final clotting enzyme, thrombin. It converts fibrinogen to fibrin which, along with the platelets, forms a clot that prevents further loss of blood and restricts entry of pathogens (Box 17.1) (Figure 17.2). 

Blood clotting first received serious scientific attention in the seventeenth century, when Malpighi and BoreUi proposed that a blood clot was formed from the fluid part of the blood. In the eighteenth century, John Hunter established that clots were formed from the coagulable lymph . In 1845, Buchanan showed that a series of enzymes was involved and by 1900 it was accepted that the soluble substance in blood, fibrinogen, was converted into the solid fibrin clot by an enzyme, thrombin. From that time many... 

Following injury to blood vessels, hemostasis ensures that blood loss is minimized. Initially, thrombocyte activation leads to contraction of the injured vessel and the formation of a loose clot consisting of thrombocytes (hemostasis). Slightly later, the action of the enzyme thrombin leads to the formation and deposition in the thrombus of polymeric fibrin (coagulation, blood clotting). The coagulation process is discussed here in detail. 

PLASMA. The portion of the blood remaining after removal of the white and red cells and the platelets it differs from serum in that it contains fibrinogen, which induces clotting by conversion into fibrin by activity of the enzyme thrombin. Plasma is made up of more than 40 proteins and also contains acids, lipids, and metal ions. It is an amber, opalescent solution in which the proteins are in colloidal suspension and the solutes (electrolytes and nonelectrolytes) are either emulsified or in true solution. The proteins can be separated from each other and from the other solutes by nltrafiltration, nltracentrifugation, electrophoresis, and immuno-chemical techniques. See also Blood. 

Heparin is a glycosaminoglycan extracted from animal tissues (porcine mucosa, beef lung, etc.). It is a mixture of molecules having a mean molecular weight of 15,000 Da. A pentasaccharide sequence found in approximately one third of the molecules binds to antithrombin in mammalian blood, enhancing its inhibitory effects on the enzymes thrombin, factor Xa, factor Vila, and factor IXa. The reaction is reversible, heparin being released after the antithrombin molecule binds to the procoagulant enzymes. Heparin binds to platelets, platelet factor-4 (which neutralizes it), histidine-rich GP vWp and a number of other proteins. Its half-life is about one hour in the circulation (18). Antibodies to heparin... 

The selective enzymatic cleavage of proteins is critical to many biological processes. For example, the clotting of blood depends on the enzyme thrombin cleaving fibrinogen at specific points to produce fibrin, the protein that forms a clot. 

Q5 The coagulation process basically involves the conversion of soluble fibrinogen into insoluble fibrin by the enzyme thrombin. 

Antithrombin-III (11) and only a portion of this, probably only one or two chains, converts Antithrombin-III into an immediate inhibitor of the enzyme thrombin (14). The chains optimal for this do not appear to be identical to those optimal for USP anticoagulant activity or to those optimal for production of inhibitor activity against other important plasma serine proteases (coagulation Factor Xa, etc.). 

The fibrinogen-to-fibrin monomer reaction is catalyzed by the proteolytic enzyme thrombin. Thrombin is in turn produced by the prothrombin-converting factors V, X, and Ca2+ from circulating prothrombin (Phase 2). Prothrombin is a globular protein made in the liver (as is fibrinogen). Vitamin K is an essential factor in its synthesis. Prothrombin-... 

Factor Xa binds to the phospholipid membranes released by platelet aggregation. Factor Xa cleaves the zymogen, prothrombin, at two specific sites to produce the active enzyme, thrombin. 

Fibrin is the protein fiber that forms a blood clot. Fibrin is produced from the precursor, fibrinogen, as the last step in a cascading series of covalent modifications of blood proteins (Figure 11.42). The enzymatic cleavage of the inactive fibrinogen to form active fibrin is catalyzed by the enzyme, thrombin. 

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