The role of the membrane in the expression of the vitamin K-dependent enzymes

Abstract

The hemostatic response to vascular damage results in the focal generation of thrombin to produce a fibrin/platelet clot at the site of vascular injury. This regulated hemostatic response derives from the assembly and activity of enzyme complexes that are localized to surfaces presented by the vascular damage. The product of each enzymatic complex provides the serine protease component required for the assembly and activity of each successive enzyme complex, ultimately leading to the formation of thrombin. When one limits attention to those complexes clearly associated with hemostatic or thrombotic risk, the significance of the vitamin K-dependent enzyme complexes becomes apparent. Each of these complexes involves a serine protease and a cofactor protein that assemble on a membrane surface in the presence of Ca++. The expression of an active complex involves, in addition to the activation of a zymogen to an enzyme, the presentation or activation of a cofactor protein and the provision of the appropriate membrane to support the reaction. The membrane plays an essential part in the formation and expression of vitamin K-dependent complexes; thus, its regulation is vital in the expression of procoagulant activity.