Proteinase inhibitor complexes, dissociation

Third, as the proteinases complete their catalysis of precursor activation, they dissociate more completely from their respective complexes and are inactivated by the proteinase inhibitors present in the blood. Dissociation from the complexes is important in the complexes and in the presence of substrates, the proteinase inhibitors are blocked from reacting with the proteinases because the substrate obstructs access to the active site of the proteinase. 

Because inactivation of factors Va and Villa by activated protein C promotes the dissociation of the pro-teinases, cofactor protein inactivation complements the action of the proteinase inhibitors. This eliminates the protection that the proteinases have when bound to their cofactor proteins and substrates. Inactivation of proteinases by SERPINS occurs via a common mechanism that involves a Michaelis complex between the proteinase and the inhibitor (Figure 36-16). This mechanism applies to all serine proteinases of the hemostatic system, i.e., the procoagulant, anticoagulant, and fibrinolytic subsystem proteinases. 

Uehara, Y., Tonomura, B., and Hiromi, K. (1978). Direct fluoro-metric determination of a dissociation constant as low as 10 0 M for the subtilisin BPN —protein proteinase inhibitor (StrepTotnyces subtilisin inhibitor) complex by a single photon counting technique. J. Biochem. (Tokyo) 84, 1195-1202. 

Like SLPI, elafin is a very potent inhibitor of NE. Elafin interacts with elastase in a reversible manner and retains its inhibitory capacity upon dissociation of the complex. Kinetic data have shown that the association rate constant for the formation of an elafin-elastase complex is pH dependent [84]. Una is probably due to the bask properties of the inhibitor and enzyme. Elafin also inhibits proteinase 3 but has no effect on cathepsin G, trypsin, or chymotrypsin. This is inloestiitg in view of the fact that SLPI inhibits cathepsin G but la relatively ineffective against proteinase 3. 

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