|The coagulation cascade initiated via tissue factor – the extrinsic pathway, or via contact – the intrinsic pathway, converges into a common pathway leading to formation of insoluble fibrin clots. Sequential activation of zymogens (inert enzyme precursors) and cofactors through limited proteolysis yields the active serine proteases and their factors. Thrombin or factor 2 (F2), the last enzyme of the cascade, cleaves fibrinogen into fibrin peptides that can polymerize. F2 also activates the protein C anticoagulant pathway and, independent of coagulation, members of protease-activated receptors (PARs). Click here to explore this complex system.
The protein C anticoagulant pathway
is an important regulatory system of the coagulation cascade. The pathway is
dependent upon activation by thrombin, or factor 2 (F2), the last enzyme of the
coagulation cascade. Binding of F2 to thrombomodulin receptor confers its
anticoagulant properties. Activated protein C, in addition to targeting
essential components of the coagulation cascade, also prompts cytoprotective
effects, outside of coagulation, by activating protease-activated receptors
(PARs). Click here to investigate this vital system.
The vitamin K cycle is part of vitamin
K metabolism and essential for the supply of a reduced form that acts as a
cofactor in the carboxylation reaction that modifies glutamate (Glu) residues
to gamma-carboxyglutamate (Gla). The modification allows for the calcium-dependent
binding of proteins known as ‘vitamin K-dependent proteins’ (VKD) to
negatively charged phospholipids of membranes. This is important for
coagulation factors and anticoagulants; their localization at/near sites of
vascular injury is crucial for proper hemostatic function. Click here to find out
more about this important metabolic pathway.