Biochemistry (Moscow)

, Volume 75, Issue 11, pp 1368–1373 | Cite as

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

  • N. A. Trushkin
  • I. S. Filimonov
  • P. V. Vrzheshch
Article
  • 38 Downloads

Abstract

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 reac- tion 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 kinet- ics 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.

Key words

prostaglandin-H-synthase cyclooxygenase activity kinetic mechanism oxygen substrate inhibition hexa-cyanoferrate(II) 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    Miyamoto, T., Ogino, N., Yamamoto, S., and Hayaishi, O. (1976) J. Biol. Chem., 251, 2629–2636.PubMedGoogle Scholar
  2. 2.
    Smith, W. L., and Marnett, L. J. (1991) Biochim. Biophys. Acta, 1083, 1–17.PubMedGoogle Scholar
  3. 3.
    Vrzheshch, P. V., and Varfolomeev, S. D. (1985) Biokhimiya, 50, 139–147.Google Scholar
  4. 4.
    Lands, W. E. M., Sauter, J., and Stone, G. W. (1978) Prostaglandins and Medicine, 1, 117–120.CrossRefPubMedGoogle Scholar
  5. 5.
    Juranek, I., Suzuki, H., and Yamamoto, S. (1999) Biochim. Biophys. Acta, 1436, 509–518.PubMedGoogle Scholar
  6. 6.
    Filimonov, I. S., and Vrzheshch, P. V. (2007) Biochemistry (Moscow), 72, 944–953.CrossRefGoogle Scholar
  7. 7.
    Vrzheshch, P. V. (1996) Biochemistry (Moscow), 61, 1481–1493.Google Scholar
  8. 8.
    Van der Ouderaa, F. J., Buytenhek, M., Nugteren, D. H., and van Dorp, D. A. (1977) Biochim. Biophys. Acta, 487, 315–331.PubMedGoogle Scholar
  9. 9.
    Falk, J. E. (1964) in Porphyrins and Metalloporphyrins, Elsevier, N.-Y., p. 181.Google Scholar
  10. 10.
    Frank, G. M., Kondrashova, M. N., Mokhova, E. N., and Rotenberg, Yu. S. (1973) Handbook on Study of Biological Oxidation by Polarography [in Russian], Nauka, Moscow.Google Scholar
  11. 11.
    Mevkh, A. T., Vrzheshch, P. V., Shvyadas, V. Yu.-K., Varfolomeev, S. D., Myagkova, G. I., and Yakusheva, L. A. (1981) Bioorg. Khim., 7, 695–702.Google Scholar
  12. 12.
    Kulmacz, R. J., Marshall, P. J., and Lands, W. E. (1987) J. Biol. Chem., 262, 3510–3517.PubMedGoogle Scholar
  13. 13.
    Tsaplina, L. A., Karatasso, Yu. O., Filimonov, I. S., and Vrzheshch, P. V. (2006) Biochemistry (Moscow), 71, 1247–1255.CrossRefGoogle Scholar
  14. 14.
    Hsuanyu, Y., and Dunford, H. B. (1992) J. Biol. Chem., 267, 17649–17657.PubMedGoogle Scholar
  15. 15.
    Dietz, R., Nastainczyk, W., and Ruf, H. H. (1988) Eur. J. Biochem., 171, 321–328.CrossRefPubMedGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2010

Authors and Affiliations

  • N. A. Trushkin
    • 1
  • I. S. Filimonov
    • 1
  • P. V. Vrzheshch
    • 1
  1. 1.International Research Center for Biochemical Technology, Faculty of Bioengineering and BioinformaticsLomonosov Moscow State UniversityMoscowRussia

Personalised recommendations