Fibrin Meshwork Formation: Proteolytic cascade
المؤلف:
Denise R. Ferrier
المصدر:
Lippincott Illustrated Reviews: Biochemistry
الجزء والصفحة:
6-1-2022
1574
Fibrin Meshwork Formation: Proteolytic cascade
The formation of the fibrin meshwork involves two unique pathways that converge to form a common pathway (Fig. 1). In each pathway, the major components are proteins (called factors [F]) designated by Roman numerals. The factors are glycoproteins that are synthesized and secreted by the liver, primarily. [Note: Several factors are also denoted by alternative names. For example, factor X (FX), the point of pathway convergence, is also known as Stuart factor.]
Figure 1: Three pathways involved in formation of the fibrin meshwork. F = factor; a = active.
Proteolytic cascade
Within the pathways, a cascade is set up in which proteins are converted from an inactive form, or zymogen, to an active form by proteolytic cleavage in which the protein product of one activation reaction initiates another. The active form of a factor is denoted by a lowercase “a” after the numeral. The active proteins FIIa, FVIIa, FIXa, FXa, FXIa, and FXIIa are enzymes that function as serine proteases with trypsin-like specificity and, therefore, cleave a peptide bond on the carboxyl side of an arginine or lysine residue in a polypeptide. For example, FIX (Christmas factor) is activated through cleavage at arginine 145 and arginine 180 by FXIa (Fig. 2). The proteolytic cascade results in enormous rate acceleration, because one active protease can produce many molecules of active product each of which, in turn, can activate many molecules of the next protein in the cascade. In some cases, activation can be caused by a conformational change in the protein in the absence of proteolysis. [Note: Nonproteolytic proteins play a role as accessory proteins (cofactors) in the pathways. FIII, FV, and FVIII are the accessory proteins.]
Figure 2: Activation of FIX (Christmas factor) via proteolysis by the serine protease FXIa. [Note: Activation can occur by conformational change for some of the factors.] F = factor; a = active; Arg = arginine.
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