Action of heparin on the inhibition of thrombin by alpha 1-proteinase inhibition.
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 thrombin neutralization was proportional to alpha 1-proteinase inhibitor concentration up to the highest concentration of inhibitor employed, 94.6 microM. The second-order rate constant under the conditions studied was 6.64 X 10(3) M-1 min-1, 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 one-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 molecular weight but not on its anticoagulant activity. Thus, in the presence of 11.7K and 22K heparins the respective rate constants are 3.5 X 10 and 1.0 X 10(3) M-1 min-1. Additionally, the concentration of heparin required to produce a maximal decrease in reaction rate depends on the molecular weight of the heparin employed.
D000818:Animals; D001798:Blood Proteins / Q000494:pharmacology*; D002417:Cattle; D006493:Heparin / Q000302:isolation & purification / Q000494:pharmacology*; D006801:Humans; D007700:Kinetics; D008168:Lung; D008970:Molecular Weight; D011480:Protease Inhibitors / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013917:Thrombin / Q000378:metabolism*; D000515:alpha 1-Antitrypsin
D001798:Blood Proteins; D011480:Protease Inhibitors; D000515:alpha 1-Antitrypsin; D006493:Heparin; D013917:Thrombin