Fibrinogen & related Peptides

A major determinant of plasma viscosity

Fibrinogen is involved in blood clot formation via its function as both a cofactor in platelet activation and a precursor of fibrin, a reaction catalyzed by thrombin. It serves as a major determinant of plasma viscosity and has been demonstrated to be an independent risk factor of cardiovascular diseases. Some studies indicate an association between fibrinogen plasma levels and the subsequent development of all the major atherosclerotic cardiovascular events, including coronary artery disease, stroke, and myocardial infarction.

Fibrinogen, a soluble plasma protein produced primarily in the liver is composed of three polypeptide chains linked together by 29 disulfide bonds and comprises of two distal regions and one central globular domain. Thrombin binds to the central domain of fibrinogen and catalyzes cleavage of two short peptides, the 16-residue fibrinopeptide A (FPA) followed by the 14-residue fibrinopeptide B (FPB), located at the N-terminus of the α and β chains, respectively.

Liberation of the fibrinopeptides exposes the central globular domain of fibrinogen resulting in the formation of fibrin monomers, which associate and cross-link to form a semi-solid network, while the fibrinopeptides remain soluble in plasma. The residual protein, fibrin monomer, polymerizes to form the fibril clot. Together with platelets, the polymerized fibrin forms a hemostatic plug.

References

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