Fibrinopeptides A and

Thrombin [EC 3.4.21.5], also known as fibrinogenase, catalyzes the hydrolysis of peptide bonds, exhibiting preferential cleavage for the Arg—Gly peptide bond. The enzyme, a member of the peptidase family SI, activates fibrinogen to fibrin and releases fibrinopeptide A and B. Thrombin, formed from prothrombin, is more selective in peptide hydrolysis than trypsin or plasmin. 

Fibrinolysis. The hydrolysis of an elastic, filamentous protein (fibrin) derived from fibrinogen by the action of thrombin, which releases fibrinopeptides A and B (co-fibrins A and B) from fibrinogen in co-agulation of the blood. 

Scheme 21 Amino Acid Sequence of a Segment of Fibrinopeptide A and Its p-Turn Peptidomimeticsl%l...

Mutations of the Bj3 chain are less common. Substitution of Cys for Gly at amino acid 15 results in prolonged polymerization from delayed release of fibrinopeptide B (Yoshida et al., 1991). Mutation of Ala68 to Thr results in defective binding of thrombin to fibrin and consequent thrombosis (Koopman et al., 1992). Deletion of residues 9-72, which includes a cysteine that is normally part of a disulfide bond, results in delayed release of both fibrinopeptides A and B (Liu et al., 1985). 

Van Hulsteijn H, Kolff J, Briet E, et al. Fibrinopeptide A and 13-thromboglobulin in patients angina pectoris and acute myocardial infarction. Am Heart J 1984 107 39—45. 

Hie serine protease thrombin takes a central position in the clotting system. It splits off fibrinopeptides A and B from the amino terminal ends of the a- and -chains of fibrinogen. The resulting fibrin monomer then undergoes polymerization to forma fibrin dot. Via activation of the clotting factors V and VIII, further thrombin is Generated from wothramhin. and via activation of blood dale lets and... 

Figure 2.30. Domain structure of fibrinogen. The fibrinogen molecule is composed of globular end regions separated from a central domain by helical threads. The central domain has cross-links that hold all the polypeptide chains together. Fibrinopeptides A and B (FPA and FPB) are found in the central domain.

Fibrinogen is a plasma protein, formed in the liver that is the basis for the formation of a blood clot. The blood concentration of this protein is about 3% and in the presence of other blood proteins pieces of the fibrinogen molecule, fibrinopeptides A and B, are cleaved and fibrinogen is polymerized to form a fibrin clot (Figure 2.30). 

Figure 5.17. Conversion of fibrinogen to fibrin. The diagram illustrates the assembly of fibrin monomer after cleavage of fibrinopeptides A and B by thrombin, causing end-to-end binding of monomers followed by lateral growth.

Figure 10.38. Structure of a Fibrinogen Molecule. (A) A ribbon diagram. The two rod regions are a-helical coiled coils, connected to a globular region at each end. (B) A schematic representation showing the positions of the fibrinopeptides A and B.

Figure 10.40. Formation of a Fibrin Clot. (1) Thrombin cleaves fibrinopeptides A and B from the central globule of fibrinogen. (2) Globular domains at the carboxyl-terminal ends of the P and y chains interact with "knobs" exposed at the amino-terminal ends of the P and a chains to form clots.

Forty patients with lung cancer, treated with a combination of cisplatin, mitomycin, vinblastine, doxorubicin, cyclosphosphamide, and methotrexate, had a significant post-treatment increase in fibrinopeptide A and a fall in fibrinolytic activity, reflected by a fall in functional tissue activator this appeared to be cumulative, depending on the extent of drug exposure (184). 

FIGURE 100-5. Pathophysiology of disseminated intravascularcoagulation. APC, activated protein C AT, antithrombin FDP, fibrin degradation products FPA, FPB, fibrinopeptides A and B PAI-1, plasminogen activator type 1 RBC, red blood cell TFPI, tissue factor pathway inhibitor. 

Elevated D-dimer Decreased antithrombin Decreased fibrinogen Thrombocytopenia Decreased protein C and protein S Increased fibrinopeptides A and B Elevated prothrombin fragments 1 and 2 Evidence of end-organ dysfunction or failure... 

Since thrombin cleaves fibrinopeptides A and B from fibrinogen, the levels of fibrinopeptides A and B should be elevated in patients with DlC. Initial studies have shown a good correlation between an elevated level of fibrinopeptide A and DlC, but other inflammatory conditions such as systemic lupus erythematosus, infections, and thrombosis may also result in elevated levels, thus decreasing the specificity of this test. Elevated prothrombin 1 and 2 indicates factor Xa generation, and is a reliable DlC marker, indicating procoagulant activation. ... 

Factor Vlll and V levels should be decreased in DlC, but results of these tests may be quite variable because of the systemic activation of the coagulation system. The most specific findings of DlC are a low platelet count associated with an elevated D-dimer level, fibrinopeptide A, and prothrombin 1 and 2, along with depressed antithrombin and fibrinogen levels. 

Fig. 2. Structure of fibrinopeptide A and reaction products formed from thrombin attack on its natural and synthetic substrate.

Batroxobin, the thrombinlike enzyme from the venom of Bothrops moojeni, is used for therapeutic defibrinogenation. In contrast to thrombin, which converts fibrinogen to fibrin by splitting off both fibrinopeptides A and B, batroxobin splits off only fibrinopeptide A. Des-A-fibrin monomers formed aggregate to atypical clots, which are trapped in the microcirculation and subsequently removed by secondary fibrinolysis and phagocytosis [27]. In case of insufficient fibrinolysis,... 

Thrombin. Fibrinogenase. 3.4.21.5 Preferential cleavage Arg-l-GIy activates fibrinogen to fibrin andreleases fibrinopeptide A and B. 

Thrombin is a serine protease in the blood coagulation cascade. The enzyme liberates fibrinopeptide A and B from fibrinogen by selectively cleaving two Arg-Gly bonds. Fibrin, the remaining portion of fibrinogen, polymerizes, forming a clot. This key role for thrombin makes inhibition of the enzyme an important target for cardiovascular research. 

The positions of fibrinopeptides A and B in the fibrinogen molecule could be deduced by sophisticated observation of the clotting process. Depending upon... 

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