Blood
Clotting
Blood clots are composed of striated fibers of a protein called fibrin. Fibrin fibers stick together in a staggered array. Before fibrin fibers can stick together, however, they must be derived from a zymogen precursor, called fibrinogen, by proteolytic cleavages that release fibrinopeptides A and B from the molecule. Removal of these small fibrinopeptides exposes sites in the fibrin molecules that allows them to stick together. Covalent cross-links between glutamine and lysine residues also form to help stabilize the structure. Thus, activation of zymogens is a key aspect to clotting of blood in vertebrates.
As can be seen in Figure 11.42, production of fibrin is the product of action of a cascade of proteases. These are summarized as follows:
In damaged tissue, the proteins kininogen and kallikrein activate factor XII (part of the intrinsic pathway).
Factor XII activates factor XI (part of the intrinsic pathway).
Alternatively, damage to blood vessels leads to release of tissue factor and activation of factor VII (start of the extrinsic pathway).
The extrinsic and intrinsic pathways merge with activation of factor X. Activation of factor X by factor IX of the intrinsic pathway requires factor VIII (antihemophilic factor).
Factor X activates prothrombin to thrombin.
Thrombin removes small fibrinopeptides from fibrinogen to form fibrin.
Note that the absence of factor VIII is the cause of classic hemophilia. Factor VIII is encoded on the X chromosome, so the disease is much more prominent in males, because they have only one X chromosome.
As wounds heal, clots must be removed. The principal agent for dissolving clots is an enzyme called plasmin, which is synthesized as the inactive zymogen called plasminogen. Plasminogen is activated by a number of proteases, the most important of which is tissue-type plasminogen activator (t-PA). t-PA can be extremely effective in initiating the cascade to dissolve the unwanted blood clot involved in stroke or heart attack.
INTERNET LINKS:
1. Clotting