P-fibrinogen

Thrombin (34 kDa), a serine protease formed by the prothrombinase complex, hydrolyzes the four Arg-Gly bonds between the fibrinopeptides and the a and P portions of the Aa and BP chains of fibrinogen (Figure 51-5A). The release of the fibrinopeptides by thrombin generates fibrin monomer, which has the subunit stmc-... 

Figure 51-5. Formation of a fibrin clot. A Thrombin-induced cleavage of Arg-Gly bonds of the Aaand B(3 chains of fibrinogen to produce fi-brinopeptides (left-hand side) and the a and p chains of fibrin monomer (right-hand side). B Cross-linking of fibrin molecules by activated factor XIII (factor Xllla).

Fig. 3. Fibrinogen molecule with its two A a, two B 3, and two -y chains. Thrombin (Ha) acts on the A a chain to generate fibrinopeptide A (FPA) and the a-chain. It also cleaves the B 3 chain to generate fibrinopeptide B (FPB) and the p-chain. S-S represents disulfide bonds. Altogether, 29 disulfide bonds hold together the six polypeptide chains that make up the fibrinogen molecule.

Lucas M. A., Fretto L. S., McKee P. A. The relationship of fibrinogen structure to plasminogen activation and plasmin activity during fibrinolysis. Ann N Y Acad Sci 1983 408, 71-91. 

Holt J. C., Mahmoud M., Gaffney P. J. The ability of fibrinogen fragments to support ADP-in-duced platelet aggregation. Thromb Res 1979 16,427-35. 

Murthy, S.N.P., Wilson, J., Guy, S.L. and Lorand, L. (1991) Intramolecular cross-linking of monomeric fibrinogen by tissue transglutaminase. Proceedings of the National Academy of Sciences USA 88, 10601-10604. 

The answer is d. (Hardman, p 1346.) A slow intravenous infusion of protamine sulfate will quickly reverse the bleeding. Protamine binds to heparin to form a stable complex with no anticoagulant activity It may also have its own anticoagulant effect by binding with platelets and fibrinogen. 

Fibrinogen (factor I) is a large (340 kDa) glycoprotein consisting of two identical tri-polypeptide units, a, P and y. Its overall structural composition may thus be represented as (a P y)2. 

Brass, O., J.M. Letoffe, A. Bakkali, J.C. Bureau, C. Corot, and P. Claudy. 1995. Involvement of protein solvation in the interaction between a contrast medium (iopamidol) and fibrinogen or lysozyme. Biophys Chem 54 83-94. 

In healthy individuals, the concentration of plasma proteins is constant. Diseases in organs that are involved in protein synthesis and breakdown can shift the protein pattern. For example, via cytokines (see p. 392), severe injuries trigger increased synthesis of acute-phase proteins, which include C-reac-tive protein, haptoglobin, fibrinogen, complement factor C-3, and others. The concentrations of individual proteins are altered in some diseases (known as dysproteinemias). 

P-Globulins Lipoprotein (LDL) Transferrin Fibrinogen Sex hormonebinding globulin Transcobalamin C-reactive protein... 

The most important reaction in blood clotting is the conversion, catalyzed by thrombin, of the soluble plasma protein fibrinogen (factor 1) into polymeric fibrin, which is deposited as a fibrous network in the primary thrombus. Thrombin (factor 11a) is a serine proteinase (see p. 176) that cleaves small peptides from fibrinogen. This exposes binding sites that spontaneously allow the fibrin molecules to aggregate into polymers. Subsequent covalent cross-linking of fibrin by a transglutaminase (factor Xlll) further stabilizes the thrombus. 

Cooper et al. [21, 22] reported in detail the results of their laborious work on the adsorption of four proteins human serum albumin (HSA), fibrinogen (FGN), fibronectin (FN), and vitronectin (VN), on five biomaterials polyethylene (PE), silicone rubber (SR), Teflon-FEP (FEP), poly(tetramethylene oxide)-poly-urethane (PTMO-PU), and polyethylene oxide)-polyurethane(PEO-PU). Hard segments of these polyurethanes are composed of a methylene-bis(p-phenylisocyanate) (MDI) chain extended wih 1,4-butanediol. 

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