Enzymes complement cascad

Complement is not a single protein but comprises a group of functionally linked proteins that interact with each other to provide mar of the effector functions of humoral immunity and inflammation. Most of the components of the system are present in the serum as proenzymes, i.e. enzyme precursors. Activation of a complement molecule occurs as a result of proteolytic cleavage of the molecule, which in itself confers proteolytic activity on the molecule. Thus, many components of the system serve as the substrate of a prior component and, in turn, activate a subsequent component. This pattern of sequential activation results in the system being called the complement cascade. ... 

FIGURE 6.9 The classical pathway of complement activation is initiated by binding of Clq to antibody on a surface such as a bacterial surface. Multiple molecules of IgG bound on the surface of a pathogen allow the binding of a single molecule of Clq to two or more Fc pieces. The binding of Clq activates the associated Clr, which becomes an active enzyme that cleaves the proenzyme Cls, generating a serine protease that initiates the classical complement cascade. 

Haruhiko, T., Kotani, S., Tanaka, S., Ogawa, T., Takahashi, I., Tsujimoto, M., Komuro, T., Shiba, T., Kusumoto, S., Kusunose, N., Hasegawa, A., Kiso, M. Structural requirements of lipid A species in activation of clotting enzymes from the horseshoe crab, and the human complement cascade. Eur J Biochem 175 (1988) 573-580. 

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. 

A number of iron-containing, ascorbate-requiring hydroxylases share a common reaction mechanism in which hydroxylation of the substrate is linked to decarboxylation of a-ketoglutarate (Figure 28-11). Many of these enzymes are involved in the modification of precursor proteins. Proline and lysine hydroxylases are required for the postsynthetic modification of procollagen to collagen, and prohne hydroxylase is also required in formation of osteocalcin and the Clq component of complement. Aspartate P-hydroxylase is required for the postsynthetic modification of the precursor of protein C, the vitamin K-dependent protease which hydrolyzes activated factor V in the blood clotting cascade. TrimethyUysine and y-butyrobetaine hydroxylases are required for the synthesis of carnitine. 

C9. Carson, S. D and Johnson, D. R., Consecutive enzyme cascades Complement activation at the cell surface triggers increased tissue factor activity. Bloodl6,361-367 (1990). 

During complement activation via the classical pathway, nine major complement components (designated C1-C9) become activated in a sequential process, the product of each activation step being an enzyme that catalyses a subsequent step in the cascade. The purpose of the cascade is twofold firstly, a sequential activation process decreases the possibility of nonspecific activation secondly, the initial response is amplified so that large numbers of complement molecules become activated in response to small amounts of initial signal. The order of events is as follows. 

Nitric oxide and eicosanoid synthesis haem synthesis. The importance of the pentose phosphate pathway reduced glutathione in maintaining red cell integrity. The respiratory burst in phagocytes. Clotting and complement enzyme cascades. Metabolism of lipoproteins. 

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. 

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