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Thromb Haemost 1971; 26(01): 103-123
DOI: 10.1055/s-0038-1653661
Originalarbeiten – Original Articles – Travaux Originaux
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Antithrombin

Inhibition of Thrombin and Autoprothrombin C (F-Xa) as a Mutual Depletion System[*]
Frederick A. Dombrose
1   Department of Physiology, Wayne State University, School of Medicine, Detroit, Michigan 48207
,
Walter H. Seegers
1   Department of Physiology, Wayne State University, School of Medicine, Detroit, Michigan 48207
,
James A. Sedensky
1   Department of Physiology, Wayne State University, School of Medicine, Detroit, Michigan 48207
› Author Affiliations
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Publication History

Publication Date:
28 June 2018 (online)

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Summary

An evaluation of the mode of action of antithrombin in the temporary inhibition of purified 3.7 S bovine thrombin was made according to traditional enzyme inhibition theory. Using enzyme clotting activity and concentration of active sites synonymously, it was observed that the binding of antithrombin to thrombin followed a second order reaction that could be distinguished into an essentially irreversible phase and a slower, potentially reversible phase. The level of steady state enzyme inhibition depended upon the ratio of the initial concentrations of enzyme to antithrombin. In addition, there occurred a rapid enhancement of enzyme esterolytic activity during the concomitant loss in clotting activity. This enhancement was also observed for acetylated thrombin which had no proteolytic activity. Under high concentrations of antithrombin, this enhancement subsequently deteriorated. A working hypothesis, including equations, for a mutual depletion system is presented to account for the known parameters of enzyme inhibition by antithrombin. We compared the neutralization of thrombin C with autoprothrombin C and found that each enzyme responds to antithrombin according to similar kinetic relationships.

This investigation supported by research grant HE-03424-14 from the National Institutes of Health, U. S. Public Health Service.


 

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