Prothrombin thrombin and

In studies related to several biological processes when esterases or other DFP-binding proteins were thought to be involved (i.e., coagulation and thrombin and prothrombin inhibition, role of lysozymes in some cardiovascular process. 

Initiation of the fibrin clot in response to tissue injury is carried out by the extrinsic pathway. How the intrinsic pathway is activated in vivo is unclear, but it involves a negatively charged surface. The intrinsic and extrinsic pathways converge in a final common path-vray involving the activation of prothrombin to thrombin and the thrombin-catalyzed cleavage of fibrinogen to form the fibrin clot. The intrinsic, extrinsic, and final common pathways are complex and involve many different proteins (Figure 51-1 and Table 51-1). In... 

Figure 51-2. Diagrammatic representation (not to scale) of the binding of factors Va, Xa, Ca +, and prothrombin to the plasma membrane of the activated platelet. The sites of cleavage of prothrombin by factor Xa are indicated by two arrows. The part of prothrombin destined to form thrombin is labeled prethrombin.The Ca " is bound to anionic phospholipids of the plasma membrane of the activated platelet.

Fig. 2. Generation of tenase and prothrombin complexes. PPL represents the anionic phospholipid surface provided by the platelets (platelet phospholipid). Cleavage of prothrombin by the prothrombinase complex results in the formation of thrombin and the release of a small fragment called prothrombin fragment 1.2 (PFI.2).

Figure 12.5 Proteolytic cleavage of prothrombin by factor Xa, yielding active thrombin. Although prothrombin is a single-chain glycoprotein, thrombin consists of two polypeptides linked by what was originally the prothrombin intrachain disulfide bond. The smaller thrombin polypeptide fragment consists of 49 amino acid residues, and the large polypeptide chain contains 259 amino acids. The N-terminal fragment released from prothrombin contains 274 amino acid residues. Activation of prothrombin by Xa does not occur in free solution, but at the site of vascular damage...

Antihemophilic factor Antihemophilic factor is a protein that converts prothrombin to thrombin, and replaces a deficit of endogenic hemophilic factor. It is synthesized by processing human plasma [69-70]. It is used to treat classic hemophilia A and to stop bleeding. Synonyms of this drug are hemophil T, monoclate, cryoblin, and others. 

Mechanism of Action A blood modifier that interferes with blood coagulation by blocking conversion of prothrombin to thrombin and fibrinogen to fibrin Therapeutic Effect Prevents further extension of existing thrombi or new clot formation. Has no effect on existing clots. 

The anticoagulant activity of heparin is endowed by its ability to form strong complexes with a variety of blood clotting factors and thus neutralize their action. For instance, heparin interacts with thrombin, fibrinogen, prothrombin, factors IX-XII... 

Heparin acts by binding to anti thrombin III, which serves as a major inhibitor of serine protease clotting enzymes. Abruptly ending heparin treatment can be hazardous because of reduced levels of antithrombin III. Coumarins, typified by warfarin, are structurally similar to vitamin K, which plays an important role in blood coagulation. By interfering with the function of vitamin K, vitamin K-dependent proteins such as clotting factors VII, IX, X and prothrombin are reduced. 

At this point there s a little twist to our developing chicken-and-egg scenario. Even activated Stuart factor can t turn on prothrombin. Stuart factor and prothrombin can be mixed in a test tube for longer than it would take a large animal to bleed to death without any noticeable production of thrombin. It turns out that another protein, called accelerin, is needed to increase the activity of Stuart factor. The dynamic duo—accelerin and activated Stuart factor— cleave prothrombin fast enough to do the bleeding animal some good. So in this step we need two separate proteins to activate one proenzyme. 

Activated platelets provides a surface for assembly of the enzyme complexes that lead to the generation of thrombin. The prothrombinase reaction results in the enzymatic conversion of prothrombin to thrombin. Prothrombinase is a complex composed of activated factor V, activated Factor X, Ca and prothrombin (Tracy and Mann, 1986 Kane and Davie, 1988). As described in 9.3.6, these sites for assembly are also present on MPs. 

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