PMID: 9173898Apr 1, 1997Paper

Prothrombinase is protected from inactivation by tissue factor pathway inhibitor: competition between prothrombin and inhibitor

The Biochemical Journal
J FranssenT Lindhout

Abstract

The inhibition of prothrombinase by tissue factor pathway inhibitor (TFPI) has been studied in the presence and absence of prothrombin. The rate constant of association of prothrombinase with full-length TFPI was 2.1x10(7) M-1.s-1 and 0.05x10(7) M-1.s-1 for the reaction with C-terminus truncated TFPI (TFPI1-161). The rate constant of dissociation was 0.65x10(-4) s-1 in both cases. The rate constant of inhibition of prothrombinase by TFPI1-161 was similar to that of solution-phase factor Xa. In contrast, phospholipids and factor Va enhanced the association rate of the reaction between factor Xa and full-length TFPI by approx. 20-fold. Although TFPI, and in particular the full-length variant of the molecule, is a potent inhibitor of prothrombinase (overall inhibition constant of 3 pM), we also found that prothrombin competed very effectively with TFPI for the active site of factor Xa in the prothrombinase complex. A 50% reduction of the rate constant of inhibition was measured in the presence of 4 nM prothrombin, i.e. 0.2% of the plasma concentration of prothrombin. The physiological significance of TFPI as an inhibitor of prothrombinase activity is thus questionable.

Citations

Jan 20, 2009·Clinics in Liver Disease·Dougald M Monroe, Maureane Hoffman
Nov 27, 2015·Thrombosis and Haemostasis·Sameera PeraramelliJan Rosing
Oct 3, 2009·Annals of the New York Academy of Sciences·Richard C BeckerBruce Sullenger
Mar 13, 2014·Blood·Jeremy P WoodAlan E Mast
Sep 17, 2002·Arteriosclerosis, Thrombosis, and Vascular Biology·Dougald M MonroeHarold R Roberts
Feb 3, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Emily L HowardRichard C Becker
Oct 16, 2013·Proceedings of the National Academy of Sciences of the United States of America·Jeremy P WoodAlan E Mast

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