TAFI, or plasma procarboxypeptidase B, couples the coagulation and fibrinolytic cascades through the thrombin-thrombomodulin complex.

The Journal of Biological Chemistry
L BajzarM Nesheim

Abstract

TAFI (thrombin-activatable fibrinolysis inhibitor) is a recently discovered plasma protein that can be activated by thrombin-catalyzed proteolysis to a carboxypeptidase B-like enzyme that inhibits fibrinolysis. This work shows that the thrombin-thrombomodulin complex, rather than free thrombin, is the most likely physiologic activator. Thrombomodulin increases the catalytic efficiency of the reaction by a factor of 1250, an effect expressed almost exclusively through an increase in kcat. The kinetics of the reaction conform to a model whereby thrombin can interact with either TAFI (Km = 1.0 microM) or thrombomodulin (Kd = 8.6 nM), and either binary complex so formed can then interact with the third component to form the ternary thrombin-thrombomodulin-TAFI complex from which activated TAFI is produced with kcat = 1.2 s-1. This work also shows that activated TAFI down-regulates tPA-induced fibrinolysis half-maximally at a concentration of 1.0 nM in a system of purified components. This concentration of TAFI is about 2% of the level of the zymogen in plasma, which indicates that ample activated TAFI could be generated to very significantly modulate fibrinolysis in vivo. Therefore, TAFI in vitro and possibly in vivo defines an exp...Continue Reading

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Citations

Aug 4, 2011·Seminars in Immunopathology·Katerina OikonomopoulouJohn D Lambris
Aug 17, 2011·Seminars in Immunopathology·Victor W M van Hinsbergh
Nov 18, 2006·Journal of Thrombosis and Thrombolysis·Xinkang WangWilliam A Schumacher
Jan 10, 2012·Journal of Thrombosis and Thrombolysis·Paul Y KimMichael E Nesheim
Oct 23, 2012·Journal of Thrombosis and Thrombolysis·Maciej BochenekAnetta Undas
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