Clotting zymogen activation

BLOOD CLOTTING. The formation of blood clots is the result of a series of zymogen activations (Figure 15.5). The amplification achieved by this cascade of enzymatic activations allows blood clotting to occur rapidly in response to injury. Seven of the clotting factors in their active form are serine proteases ... 

During blood clot formation a complex cascade of zymogen activation occurs, whereby each currently activated zymogen activates the subsequent zymogen. For details one is referred to text books. 

Interactions between serine proteases are common, and substrates of serine proteases are usually other serine proteases that are activated from an inactive precursor [66]. The involvement of serine proteases in cascade pathways is well documented. One important example is the blood coagulation cascade. Blood clots are formed by a series of zymogen activations. In this enzymatic cascade, the activated form of one factor catalyzes the activation of the next factor. Very small amounts of the initial factors are sufficient to trigger the cascade because of the catalytic nature of the process. These numerous steps yield a large amplification, thus ensuring a rapid and amplified response to trauma. A similar mechanism is involved in the dissolution of blood clots. A third important example of the coordinated action of serine proteases is the intestinal digestive enzymes. The apoptosis pathway is another important example of coordinated action of other types of proteases. 

Blood Clotting Is Accomplished by a Cascade of Zymogen Activations... 

This includes both reversible changes like phosphorylation of specific serines in the enzymes of glycogen metabolism and irreversible changes like zymogen activation by proteolysis in digestion and blood clotting. These mechanisms are considered in more detail below. 

Blood clotting is a situation in which the enzymes needed to form a clot must be present in the blood and ready to act rapidly when trauma to a blood vessel occurs. However, clots must not form in normal blood vessels or a heart attack or stroke will occur. The blood-clotting system is a complex and highly regulated mechanism which uses many steps of zymogen activation, with more examples of serine proteases. 

Zymogen activations may be linked to form a cascade, such as that involved in blood clotting. 

The clotting of blood occurs by a series of zymogen activations. Why are the enzymes that catalyze blood clotting produced as zymogens ... 

Figure 12.11 (a) The fibrinolytic system, in which tPA proteolytically converts the zymogen plasminogen into active plasmin, which in turn degrades the fibrin strands, thus dissolving the clot. tPA and plasminogen both bind to the surface of fibrin strands (b), thus ensuring rapid and efficient activation of the thrombolytic process... 

The blood coagulation cascade. Each of the curved red arrows represents a proteolytic reaction, in which a protein is cleaved at one or more specific sites. With the exception of fibrinogen, the substrate in each reaction is an inactive zymogen except for fibrin, each product is an active protease that proceeds to cleave another member in the series. Many of the steps also depend on interactions of the proteins with Ca2+ ions and phospholipids. The cascade starts when factor XII and prekallikrein come into contact with materials that are released or exposed in injured tissue. (The exact nature of these materials is still not fully clear.) When thrombin cleaves fibrinogen at several points, the trimmed protein (fibrin) polymerizes to form a clot. 

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