Action of heparin on the inhibition of thrombin by .alpha.1-proteinase inhibitor

Publisher Website
Google Scholar
Abstract
.alpha.1-Proteinase inhibitor inhibits the action of thrombin while heparin is effective in relieving this inhibition. Kinetic analyses of the inhibition in the absence and presence of heparin were conducted by employing the p-nitroanilide of a synthetic peptide, S-2238, to determine residual thrombin activity. Under pseudo-first-order conditions, the rate of [human] thrombin neutralization was proportional to .alpha.1-proteinase inhibitor concentration up to the highest concentration of inhibitor employed, 94.6 .mu.M. The 2nd-order rate constant under the conditions studied was 6.64 .times. 103 M-1 min--, and heparin was found to cause a decrease in the rate constant. On the basis of the concentrations used, the kinetics of thrombin inhibition, both in the absence and in the presence of heparin, can be described by a 1-step reaction. The effect of heparin is due to its binding to thrombin. The degree to which heparin interferes with the rate of thrombin inhibition depends on its MW but not on its anticoagulant activity. Thus, in the presence of 11.7K [kilodalton] and 22K heparins the respective rate constants are 3.5 .times. 10 and 1.0 .times. 103 M-1 min-1. Additionally, the concentration of heparin required to produce a maximal decrease in reaction rate depends on the MW of the heparin employed.