Effect of heparin on thrombin inactivation by antithrombin-III

R. Machovich, P. Aranyi

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Abstract

The inactivation of thrombin by heat and by its physiological inhibitor, antithrombin-III, shows quite different dependence on heparin concentration. Heparin at 250 μg/ml protects thrombin against heat inactivation, and thrombin behaves heterogeneously in this reaction. In the absence of heparin, the thermodynamic activation parameters change with temperature (ΔH≠ = 733kJ/mol and 210kJ/mol at 50 and 58°C respectively). When heparin is present, heat inactivation of the protected thrombin species proceeds with ΔH≠ = 88kJ/mol and is independent of temperature in the same range. On the other hand, heparin at 0.125-2.5 μg/ml accelerates the thrombin-antithrombin-III reaction. Thrombin does not show heterogeneity in this reaction and the time courses at any heparin concentration and any temperature between 0 and 37°C appear to follow first-order kinetics. Activation enthalpy is independent of heparin concentration or temperature, ΔH≠ = 82-101kJ/mol, varying slightly with antithrombin-III concentration and thrombin specific activity. Heparin seems to exert its effect by increasing activation entropy. On the basis of these data we suggest a mechanism of action of heparin in the thrombin-antithrombin-III reaction which accounts for all the important features of the latter and seems to unify the different hypotheses that have been advanced.

Original languageEnglish
Pages (from-to)869-875
Number of pages7
JournalBiochemical Journal
Volume173
Issue number3
DOIs
Publication statusPublished - Jan 1 1978

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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