Comparison of the inhibition of thrombin by three plasma protease inhibitors

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Abstract
Human .alpha.-thrombin is inhibited by the circulating protease inhibitors .alpha.1-antitrypsin, antithrombin III and .alpha.2-macroglobulin. Kinetic analyses of the inhibitor thrombin interactions were carried out utilizing fibrinogen or the synthetic substrate Bz-Phe-Val-Arg p-nitroanilide as substrates to determine residual thrombin activity. The inhibition of thrombin by .alpha.1-antitrypsin, antithrombin III, and .alpha.2-macroglobulin apparently followed 2nd-order kinetics. The rate constants for the inhibition of thrombin by .alpha.1-antitrypsin, antithrombin III and .alpha.2-macroglobulin were 6.51 .+-. 0.38 .times. 103, 3.36 .+-. 0.34 .times. 105 and 2.93 .+-. 0.02 .times. 104 M-1 min-1, respectively. Comparison of the 2nd-order rate constants and the normal plasma levels of the 3 inhibitors demonstrated that, under the in vitro conditions utilized, antithrombin III is 5 times and .alpha.2-macroglobulin is 1/3 as effective as .alpha.1-antitrypsin in the inhibition of thrombin.