Fibrin monomer

Fibrin is an elastic filamentous protein elaborated from its precursor, fibrinogen, which is present in plasma at high concentration. Fibrin is formed in response to the actions of thrombin. Thrombin cleaves small peptides from the fibrinogen molecule, forming fibrin monomers that will begin to polymerize and become crosslinked. 

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).

Endres GF, Ehrenpreis S, Scheraga HA. Covalent bonding in the reversible polymerization of fibrin monomer. Biochim Biophys Acta 1965 104 620-623. 

Induction of the blood coagulation cascade. This culminates in the conversion of a soluble serum protein, fibrinogen, into insoluble fibrin. Fibrin monomers then aggregate at the site of... 

Figure 17.2 The intrinsic and extrinsic pathways involved in blood clotting. Both pathways converge to activate thrombin. Solid arrows represent biochemical conversions whereas dotted arrows represent either catalytic or activating actions. Fibrin is formed as monomers which polymerise to form fibrils. Within the fibrils, the fibrin monomers associate laterally which is facilitated by active XIII (ie Xllla). Thrombin activates XIII.

Fibrin polymerization is initiated by the enzymatic cleavage of the fibrinopeptides, converting fibrinogen to fibrin monomer (Fig. 1). Then, several nonenzymatic reactions yield an orderly sequence of macromolec-ular assembly steps. Several other plasma proteins bind specifically to the resulting fibrin network. The clot is stabilized by covalent ligation or crosslinking of specific amino acids by a transglutaminase, Factor XHIa. 

Specific interactions between the A a complementary binding sites produce aggregates in which the fibrin monomers are half-staggered, since the central domain of one molecule binds to the end of the adjacent molecule (Fig. 5). Initially, a dimer is formed and then additional molecules are added to give a structure called the two-stranded protofibril (Fig. 3B) (Fowler et ai, 1981 Medved et ai, 1990). 

Interactions between fibrin and fibrinogen are likely to be important during early stages of polymerization, when fibrin monomers are... 

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... 

Id vivo, the infusion of small amounts of thrombin (<200 NIH-U/kg/h) causes defibrinogenation. Because of the slow transformation of fibrinogen, the fibrin monomers formed are eliminated via reactive fibrinolysis and RES without precipitation of fibrin. Upon infusion of higher amounts of thrombin, these clearance mechanisms fail bo offset the thrombin action, which then leads to the formation of microthmmbi in the peripheral circulation. Correspondingly, the bolus injection of 1500 NIH-U thrombin/kg caused death of the experimental... 

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.

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