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The interaction of heparin with thrombin and antithrombin

1980; Elsevier BV; Volume: 96; Issue: 3 Linguagem: Inglês

10.1016/0006-291x(80)90079-0

1090-2104

Robert Rosenberg, G.M. Oosta, Robert E. Jordan, W.T. Gardner,

Blood properties and coagulation

We have monitored the binding of heparin to thrombin as well as antithrombin by fluorescence techniques. The interaction of mucopolysaccharide with thrombin is characterized by a stoichiometry of 2:1 with KDISSH1T = KDISSH2T = 8 × 10−7 M. The interaction of heparin with antithrombin is typified by a stoichiometry of 1:1 with KDISSH-A = 5.7 × 10−8 M. A plot of the initial velocity of the thrombin-antithrombin reaction versus mucopolysaccharide concentration exhibits an ascending limb, descending limb and final plateau. The ascending limb of the kinetic profile corresponds to the level of heparin-antithrombin complex. The descending limb of the initial velocity plot coincides with the formation of tertiary complexes between two molecules of heparin and one molecule of thrombin. Thus, our data demonstrates that the generation of heparin-antithrombin complex is responsible for the mucopolysaccharide dependent acceleration of enzyme neutralization. Furthermore, our results also suggest that interactions between heparin bound to inhibitor and free enzyme can account for only a small fraction of the total kinetic effect of the complex carbohydrate. Therefore, we conclude that the direct binding of heparin to antithrombin is probably responsible for the anticoagulant effect of the mucopolysaccharide.