Biochemistry (Moscow)

, Volume 71, Issue 11, pp 1247–1255 | Cite as

Kinetic mechanism of the bifunctional enzyme prostaglandin-H-synthase. Effect of electron donors on the cyclooxygenase reaction

  • L. A. Tsaplina
  • Yu. O. Karatasso
  • I. S. Filimonov
  • P. V. Vrzheshch
Article

Abstract

Prostaglandin-H-synthase (PGHS, EC 1.14.99.1) catalyzes the first committed step in biosynthesis of all prostaglandins, thromboxanes, and prostacyclins by converting arachidonic acid to prostaglandin H2 (PGH2). PGHS exhibits two enzymatic activities: cyclooxygenase activity converting arachidonic acid to prostaglandin G2 (PGG2) and peroxidase activity reducing the hydroperoxide PGG2 to the corresponding alcohol, PGH2. Despite the many investigations of the kinetics of PGHS, many features such as the absence of competition and mutual activation between the cyclooxygenase and peroxidase activities cannot be explained in terms of existing schemes. In this work we have studied the influence of different electron donors (N,N,N′,N′-tetramethyl-p-phenylenediamine, L-epinephrine, 2,2′-azinobis(3-ethylbenzthiazoline-6-sulfonic acid), potassium ferrocyanide) on the PGHS activities. The proposed scheme describes independent but interconnected cyclooxygenase and peroxidase activities of PGHS. It also explains the experimental data obtained in the present work and known from the literature.

Key words

prostaglandin-H-synthase bifunctional enzyme cyclooxygenase activity kinetic mechanism inhibition naproxen TMPD 

Abbreviations

AA

arachidonic acid

ABTS

2,2′-azinobis(3-ethylbenzthiazoline-6-sulfonic acid

COX

cyclooxygenase

DEDTC

diethyldithiocarbamate

PGHS

prostaglandin-H-synthase

PGG2

prostaglandin G2

PGH2

prostaglandin H2

PPIX

protoporphyrin IX

ROH

general formula for alcohols

ROOH

general formula for peroxides

TMPD

N,N,N′,N′-tetramethyl-p-phenylenediamine

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Copyright information

© Pleiades Publishing, Inc. 2006

Authors and Affiliations

  • L. A. Tsaplina
    • 1
    • 3
  • Yu. O. Karatasso
    • 1
    • 2
  • I. S. Filimonov
    • 1
    • 2
  • P. V. Vrzheshch
    • 1
    • 3
  1. 1.Department of Bioengineering and BioinformaticsLomonosov Moscow State UniversityMoscowRussia
  2. 2.Emanuel Institute of Biochemical PhysicsRussian Academy of SciencesMoscowRussia
  3. 3.International Biotechnological CenterLomonosov Moscow State UniversityMoscowRussia

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