Question

The complement system functions by series of cleavage and conversion. What role does C3 convertase and c5 convertase play in the complement system. Provide detailed answer

Answer 1

Complement is essential for the protection against infections but dysregulation of complement activation can cause onset and progression of numerous inflammatory diseases. Convertase enzymes play a central role in complement activation and produce the key mediators of complement. C3 convertases cleave C3 to generate chemoattractant C3a and label target cells with C3b, which promotes phagocytosis; C5 convertases cleave C5 into chemoattractant C5a, and C5b, which drives formation of the membrane attack complex.

C3 convertase which is generated during the first stage of complement activation, cleaves C3, the central and most abundant component of the complement system. This proteolytic cleavage leads to formation of a smaller C3a fragment and a larger C3b fragment. The formation of C3 convertase can occur through three different pathways which are the classical, lectin, and alternative pathways. C3a is a soluble polypeptide and thus diffuses away while C3b molecules, if not hydrolyzed and inactivated in the fluid phase, can form covalent bonds with the surface of microbial pathogens or immune complexes and activate the complement system. The C3b molecules associate with C4bC2a or C3bBb complexes to form the C5 convertase. The C5 convertase cleaves C5 and initiates activation and assembly of the terminal components, C5, C6, C7, C8, and C9, into the C_5b-9 membrane attack complex (MAC; also known as terminal complement complex [TCC]) on the surface of foreign pathogens. Selective inhibition of C3 and C5 convertases is of great therapeutic interest.