Anticoagulant subsystem

It is helpful in the effort to understand activation complexes to consider complex formation, the reactions that occur in the complexes, and the demise of the complexes as proceeding in a sequence. First, a reversible, noncovalent association of proteinase, cofactor protein (strictly, activated cofactor protein), proteinase precursor, and membrane surface occurs to form the activation complex. This spontaneous association occurs as the result of complementary interaction sites on the protein molecules, e.g., the binding sites between proteinase and protein substrate, proteinase and cofactor protein, substrate and cofactor protein, and all three proteins with the membrane surface. Tissue factor normally exists as an integral membrane protein and is always associated with the membranes of cells in the vessel wall. The same processes are involved in the anticoagulant subsystem and, with a different surface, fibrin in the fibrinolytic system as well. 

SECTION 36.8 Anticoagulant Subsystem—Activation of Protein C and Inactivation of Factors Va and Villa... 

Plasma Coagulation Factors—Anticoagulant Subsystem Components... 

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. 

---