Proteolysis blood coagulation

As in blood coagulation (see p. 290), the early components in the complement system are serine proteinoses, which mutually activate each other through limited proteolysis. They create a self-reinforcing enzyme cascade. Factor C3, the products of which are involved in several functions, is central to the complement system. 

The enzymes that participate in blood clotting also are activated by partial proteolysis, which again serves to keep them in check until they are needed. The blood coagulation system involves a cascade of at least seven serine proteases, each of which activates the subsequent enzyme in the series (fig. 9.2). Because each molecule of activated enzyme can, in turn, activate many molecules of the next enzyme, initiation of the process by factors that are exposed in damaged tissue leads explosively to the conversion of prothrombin to thrombin, the final serine protease in the series. Thrombin then cuts another protein, fibrin, into peptides that stick together to form a clot. 

Partial proteolysis, an irreversible process, is used to activate proteases and other digestive enzymes after their secretion and to switch on enzymes that cause blood coagulation. Common types of reversible covalent modification include phosphorylation, adenylyla-tion, and disulfide reduction. 

Protein C functions as an anticoagulant by proteolytically inactivating two protein cofactors of blood coagulation, factors V and VIII.402 It too circulates in a zymogen form and is activated by limited proteolysis. Protein C appears to contain about 16 sites for Ca2+, all of equal affinity, while activated protein C binds about nine Ca2+. Conformational rearrangement during activation results in loss of binding sites. 

Figure 6. Triggering of kinin formation, blood coagulation, and fibrinolysis through specific proteolytic activation of the Hageman Factor (Factor XII). In the cascades, the factor on the left side of the reaction (zymogen) is converted to an active enzyme by proteolysis. PL = phospholipids.

A series of proteins collectively called the complement participate in the immune response to the entry of foreign cellular or viral material into the organism. This group of proteins consists of about 20 entities, some of which are enzymes. Complement was first associated with the lysis of foreign red blood cells in the nineteenth century it also participates in the lysis of bacterial cells. The complement activation cascade, very similar to the blood coagulation cascade, involves the stepwise activation, via proteolysis, of various components of the complement system until a final protein complex, the membrane attack unit (also called the C5b-9 complex), is generated. It then punches holes in the membrane to which it is bound. 

Proteolysis in the cascade system of Blood coagulation (see) (see Prothrombin). 

Tphe kinetics of the protease-triggered clotting of blood and milk has been formulated in a number of recent publications from this laboratory (1,2,3). In milk clotting, the coagulation is initiated through the limited proteolysis of -casein, the milk protein component which normally protects the casein micelles from flocculation by calcium ions (4). Kappa-casein is a single polypeptide chain of 169 residues, the sequence... 

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