Inhibition of Cyclooxygenase Activity of Prostaglandin-H-Synthase by Excess Substrate (Molecular Oxygen)

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N. A. Trushkin, I. S. Filimonov, and P. V. Vrzheshch^*

International Research Center for Biochemical Technology, Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119992 Moscow, Russia; fax: (495) 939-5022; E-mail: peter@genebee.msu.ru

^* To whom correspondence should be addressed.

Received April 3, 2010; Revision received June 17, 2010

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For the cyclooxygenase reaction of prostaglandin-H-synthase isolated from ram vesicular glands, dependences of the initial reaction rate, the maximal yield of the product, and the rate constant of enzyme inactivation in the course of reaction on oxygen concentration were studied in the absence and in the presence of electron donor in the reaction medium. It is shown that in the absence of electron donor the cyclooxygenase reaction is strictly governed by Michaelis–Menten kinetics over a wide range of oxygen concentrations (5-800 µM). In the presence of electron donor in the reaction medium it was found that cyclooxygenase reaction is inhibited by an excess of dissolved oxygen: the maximal values of the initial reaction rate and yield of the product are attained at oxygen concentration 50 µM, and its increase to 500 µM causes twofold decrease in the initial rate and maximal yield. The rate constant of enzyme inactivation in the course of reaction increases on increase in oxygen concentration both in the presence and in the absence of electron donor.

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KEY WORDS: prostaglandin-H-synthase, cyclooxygenase activity, kinetic mechanism, oxygen, substrate inhibition, hexacyanoferrate(II)

DOI: 10.1134/S0006297910110088

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