Series reactions blood clotting

Clotting cascade A series of enzymatic reactions by clotting factors leading to the formation of a blood clot. The clotting cascade is initiated by several thrombogenic substances. Each reaction in the cascade is triggered by the preceding one, and the effect is amplified by positive feedback loops. 

Blood coagulation. The third major step in hemostasis is coagulation, or the formation of a blood clot. This complex process involves a series of reactions that result in formation of a protein fiber meshwork that stabilizes the platelet plug. Three essential steps lead to clotting (see Figure 16.1) ... 

Blood coagulation, which takes place at the site of an injury or in response to exposure to a foreign surface, is triggered by a series of enzymatic reactions that culminate in the production of the enzyme thrombin. Thrombin is responsible for the formation of fibrin, which together with the platelets present in blood is a key ingredient of a blood clot. Most of these events take place at the contact site. 

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. 

Research in many different laboratories has shown that the clotting of blood results from two series of stepwise reactions ultimately leading to the formation of a tough insoluble fibrin clot (1,2). Depending on the mechanism of activation, two clotting cascades can occur (Figure 1). Exposure to a foreign... 

Release of thrombin fi-om its inactive zymogen. Prothrombin (see), is the penultimate step in a series of reactions, each of which releases an active serine protease from an inactive precursor in the blood. It is an example of cascade regulation, in which each activated protease activates the next precursor down the line, increasing amounts of material being involved at each step (i.e. there is amplification). The clotting factors are listed in the Table. The assigned Roman numerals are historical, and the activated form is indicated by the subscript a (e.g. XII,). 

For a clot to be formed, sufficient thrombin (Factor Ila) must be present at the site of injury but, at the same time, active clotting factors cannot circulate in the blood in concentrations that would allow clotting to occur. The dilemma is solved by having many of the clotting factors present in an inactive precursor form which is activated only as and when required. The clotting process is an enzyme cascade involving a series of hydrolytic reactions in which the product of one reaction acts as the enzyme for the next. 

A series of reactions involving six proteins causes blood to clot. The process requires these proteins to bind Ca ". y-Carboxyglutamates bind Ca much more effectively than glutamates do. 

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