Comparison of the inhibition of thrombin by three plasma protease inhibitors.
Human alpha-thrombin is inhibited by the circulating protease inhibitors alpha1-antitrypsin, antithrombin III, and alpha2-macroglobulin. Kinetic analyses of the inhibitor thrombin interactions were carried out utilizing either fibrinogen or the synthetic substrate Bz-Phe-Val-Arg-p-nitroanilide as substrates to determine residual thrombin activity. These studies demonstrated that the inhibition of thrombin by alpha1-antitrypsin, antithrombin III, and alpha2-macroglobulin followed second-order kinetics. The rate constants for the inhibition of thrombin by alpha1-antitrypsin, antithrombin III, and alpha2-macroglobulin are 6.51 +/- 0.38 x 10(3), 3.36 +/- 0.34 x 10(5), and 2.93 +/- 0.02 x 10(4) M-1 min-1, respectively. Comparison of the second-order rate constants and the normal plasma levels of the three inhibitors demonstrates that, under the in vitro conditions utilized, antithrombin III is five times and alpha2-macroglobulin is one-third as effective as alpha1-antitrypsin in the inhibition of thrombin.
D000990:Antithrombin III / Q000502:physiology; D004791:Enzyme Inhibitors / Q000097:blood*; D006801:Humans; D007700:Kinetics; D013917:Thrombin / Q000037:antagonists & inhibitors*; D000515:alpha 1-Antitrypsin / Q000502:physiology; D000511:alpha-Macroglobulins / Q000502:physiology
D004791:Enzyme Inhibitors; D000515:alpha 1-Antitrypsin; D000511:alpha-Macroglobulins; D000990:Antithrombin III; D013917:Thrombin