Molecular Oxygen (a Substrate of the Cyclooxygenase Reaction) in the Kinetic Mechanism of the Bifunctional Enzyme Prostaglandin-H-synthase

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I. S. Filimonov^1,2 and P. V. Vrzheshch^1,3*

¹Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119992 Moscow, Russia; fax: (495) 939-4218; E-mail: peter@genebee.msu.ru

²Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, ul. Kosygina 4, 117997 Moscow, Russia; fax: (495) 137-4101; E-mail: asp@sky.chph.ras.ru

³International Biotechnological Center, Lomonosov Moscow State University, 119992 Moscow, Russia; fax: (495) 939-5022

^* To whom correspondence should be addressed.

Received March 31, 2007; Revision received May 26, 2007

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Prostaglandin-H-synthase is a bifunctional enzyme catalyzing conversion of arachidonic acid into prostaglandin H₂ as a result of cyclooxygenase and peroxidase reactions. The dependence of the rate of the cyclooxygenase reaction on oxygen concentration in the absence and in the presence of electron donor was determined. A two-dimensional kinetic scheme accounting for independent proceeding and mutual influence of the cyclooxygenase and peroxidase reactions and also for hierarchy of the rates of these reactions was used as a model. In the context of this model, it was shown that there are irreversible stages in the mechanism of the cyclooxygenase reaction between points of substrate donation (between donation of arachidonic acid and the first oxygen molecule and also between donation of two oxygen molecules).

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KEY WORDS: prostaglandin-H-synthase, bifunctional enzyme, cyclooxygenase activity, kinetic mechanism, oxygen, arachidonic acid, adrenaline

DOI: 10.1134/S0006297907090040

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