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Molecular oxygen (a substrate of the cyclooxygenase reaction) in the kinetic mechanism of the bifunctional enzyme prostaglandin-H-synthase

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Abstract

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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Abbreviations

AA:

arachidonic acid

D:

oxidized form of electron donor

DH:

reduced form of electron donor

PGG2 :

prostaglandin G2

PGH2 :

prostaglandin H2

PGHS:

prostaglandin-H-synthase

PP:

protoporphyrin IX

ROOH:

peroxide

Tyr:

tyrosine residue

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Authors and Affiliations

  1. Faculty of Bioengineering and Bioinformatics, Lomonosov Moscow State University, 119992, Moscow, Russia

    I. S. Filimonov & P. V. Vrzheshch

  2. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, ul. Kosygina 4, 117997, Moscow, Russia

    I. S. Filimonov

  3. International Biotechnological Center, Lomonosov Moscow State University, 119992, Moscow, Russia

    P. V. Vrzheshch

Authors
  1. I. S. Filimonov
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  2. P. V. Vrzheshch
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Correspondence to P. V. Vrzheshch.

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Original Russian Text © I. S. Filimonov, P. V. Vrzheshch, 2007, published in Biokhimiya, 2007, Vol. 72, No. 9, pp. 1161–1171.

Originally published in Biochemistry (Moscow) On-Line Papers in Press, as Manuscript BM07-088, August 5, 2007.

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Filimonov, I.S., Vrzheshch, P.V. Molecular oxygen (a substrate of the cyclooxygenase reaction) in the kinetic mechanism of the bifunctional enzyme prostaglandin-H-synthase. Biochemistry Moscow 72, 944–953 (2007). https://doi.org/10.1134/S0006297907090040

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  • DOI: https://doi.org/10.1134/S0006297907090040

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