Thrombin (EC184.108.40.206, ÃŽÂ±-thrombin) is the product of proteolytic activation of the zymogen prothrombin.Ã‚Â Human thrombin is a two-chain serine protease with a mass of 37 kDa.Ã‚Â The active site is located within the heavy chain.Ã‚Â Thrombin has a high specificity for certain arginine bonds in protein substrates.Ã‚Â The primary substrate is fibrinogen which thrombin converts to fibrin through the cleavage of four arginyl-glycyl peptide bonds.Ã‚Â Thrombin is also an important activator of platelets, factor XIII, Protein C and TAFI (Plasma procarboxypeptidase B).Ã‚Â In a positive feedback mechanism, thrombin increases the rate of its own production by activation of factors VIII and V.Ã‚Â The rate of thrombin production is subsequently limited indirectly through the activation of Protein C by thrombin, which then inactivates the activated cofactors VIII and V.Ã‚Â The binding of thrombin to thrombomodulin on the cell surface dramatically alters thrombinÃ¢â‚¬â„¢s specificity, increasing itÃ¢â‚¬â„¢s activity toward Protein C and TAFI, and decreasing itÃ¢â‚¬â„¢s activity toward fibrinogen and activating cofactors VIII and V.Ã‚Â In plasma, thrombin activity is inhibited primarily by antithrombin and to a lesser extent heparin cofactor II.Ã‚Â The rate of inhibition by both of these inhibitors is profoundly increased in the presence of optimal concentrations of heparin.Ã‚Â Other physiological inhibitors of thrombin in the absence of heparin include ÃŽÂ±2-macroglobulin and ÃŽÂ±1-antitrypsin1-4.
References and Reviews
Mann KG; Prothrombin and Thrombin; in Hemostasis and Thrombosis, 3rd Edition, eds. RW Colman, J Hirsh, VJ Marder and EW Salzman, pp. 184-199, J.B. Lippincott Co., Philadelphia PA, USA, 1994.
Stubbs MT, Bode W; A Player of Many Parts: The Spotlight Falls on ThrombinÃ¢â‚¬â„¢s Structure; Thrombosis Research 69, pp 1-58, 1993
Downing MW, Bloom JW, Mann KG; Comparison of the Inhibition of Thrombin by Three Plasma Protease Inhibitors; Biochemistry 17, pp 2649-2653, 1978.
Weitz JI, Hudoba M, Massel D, Maranganore J, Hirsh J; Clot-bound Thrombin is Protected from Inhibition by Heparin-ATIII but is Susceptible to – ATIII independent Inhibitors; J. Clin. Invest 86, pp 385-391, 1990.