Blood coagulation cascade mechanism

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. 

Fig. 10. Schematic presentation of blood coagulation cascade (A) and the activation mechanism of Factor VIII (B).

Regulatory mechanisms within the blood coagulation cascade and antifibrinolytic mechanisms prevent random coagulation within blood vessels that might obstruct blood flow. Impairments in these mechanisms lead to thrombosis. 

A proteolytic cascade occurs when one peptidase activates the next in a proteolytic pathway, and this in turn activates the next and so on. This is a mechanism to amplify the initial signal, because one peptidase molecule can activate many zymogen molecules. Examples of proteolytic cascades include blood coagulation, activation of digestive peptidases in the intestine, and apoptosis. 

The concept that different structural domains on the heparin chains are principally involved for optimal activity in the foregoing interactions could not be perceived in early work on structure-activity correlations, because the activity of heparin has been most frequently evaluated only with whole-blood-clotting tests (such as the U.S.P. assay). Development of assays for specific clotting-factors (especially Factor Xa and thrombin) has permitted a better insight into the mechanism of action of heparin at different levels of the coagulation cascade. 

Blood coagulation resulting in the formation of a stable fibrin clot involves a cascade of proteolytic reactions involving the interaction of clotting factors, platelets, and tissue materials. Clotting factors (see table) exist in the blood in inactive form and must be converted to an enzymatic or activated form before the next step in the clotting mechanism can be stimulated. Each factor is stimulated in turn until an insoluble fibrin clot is formed. 

Thrombus versus embolus A clot that adheres to a vessel wall is called a thrombus, whereas an intravascular clot that floats within the blood is termed an embolus. Thus, a detached thrombus becomes an embolus. Both thrombi and emboli are dangerous, because they may occlude blood vessels and deprive tissues of oxygen and nutrients. Arterial thrombosis most often involves medium-sized vessels rendered thrombogenic by surface lesions of endothelial cells caused by atherosclerosis. In contrast, venous thrombosis is triggered by blood stasis or inappropriate activation of the coagulation cascade, often as a result of a defect in the normal defense hemostatic mechanisms. 

Several vital processes rely on clan PA peptidases. Chief among them are blood coagulation and the immune response, which involve cascades of sequential zymogen activation. In both systems, the chymotrypsin-fold peptidase domain is combined with one more associated protein domains, including apple, CUB, EGF, fibronectin, kringle, sushi, and von Willebrand factor domains. These protein domains are on the N-terminus as an extension of the propeptide segment of the peptidase. Such a trend of N-terminal-associated domains in the SIA peptidase family is common across all forms of life. The domain architecture pairs well with the zymogen activation mechanism, which liberates the proper N-terminus to enable catalytic activity. Often, the associated protein domains remain attached to... 

The presence of Calcium (Ca ) is necessary for blood coagulation and subsequently prevents hemorrhaging from tissue injuries. The mechanism consists of cascade-type process in which stages are connected with the presence of Ca. Many of the so-called factors of blood coagulation are well known. Vitamin K is necessary in the biosynthesis of the factors IX, X, and VII and of prothrombin. The 1,25-dioxiform of vitamin D3 facilitates the process of Ca reception from the intestines. Accumulation of Ca and its release from humans is a complex system, and also includes vitamin D. 

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