Kinetic Basis for the Impaired Oxygenation of Eicosapentaenoate by Prostaglandin Endoperoxide Synthase

  • R. B. Pendleton
  • W. E. M. Lands
Part of the Developments in Oncology book series (DION, volume 67)


Prostaglandin endoperoxide synthase (PES) oxygenates certain 20-carbon polyunsaturated fatty acids as the first committed step in the biosynthesis of prostaglandins. Both steroidal and non-steroidal anti-inflammatory agents inhibit prostaglandin biosynthesis, and therefore, it has been postulated that prostaglandin overproduction may be a pathophysiologic mechanism common to a number of chronic inflammatory and thromboembolic diseases. Epidemiologic studies have shown that many eicosanoidrelated diseases are prevalent in populations that consume large amounts of n-6 polyunsaturated fatty acids (n-6 PUFA), but less frequent in populations that consume large amounts of n-3 PUFA. As neither n-3 nor n-6 PUFA can be synthesized de novo in human tissues, the common substrate acids for prostaglandin biosynthesis must be derived from the diet. The n-3 PUFA, 5,8,11,14,17-eicosapentaenoic acid (20:5n-3), is a less effective substrate for PES than the n-6 PUFA, 5,8,11,14-eicosatetraenoic acid (20:4n-6 or arachidonate). Therefore, it has also been postulated that the overproduction of prostaglandins may be inhibited by dietary n-3 polyunsaturated fatty acids [1].


Polyunsaturated Fatty Acid Kinetic Rate Constant Prostaglandin Biosynthesis Cyclooxygenase Activity Impaired Oxygenation 
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  1. 1.
    W.E.M. Lands. 1986. Fish and Human Health. Academic Press, Orlando, FL.Google Scholar
  2. 2.
    Stubbe, J.A. 1989. Protein Radical Involvement in Biological Catalysis? Annu. Rev. Biochem., 58, 257–285.PubMedCrossRefGoogle Scholar
  3. 3.
    Kulmacz, R.J., Miller, J.F. Jr., and Lands, W.E.M. 1985. Prostaglandin H Synthase: An Example of Enzymic Symbiosis. Biochem. Biophys. Res. Commun., 130, 918–923.Google Scholar
  4. 4.
    Kulmacz, R.J. 1987. Prostaglandin G2 Levels During Reaction of Prostaglandin H Synthase with Arachidonic Acid. Prostaglandins, 34, 225–240.PubMedCrossRefGoogle Scholar
  5. 5.
    Barshop, B.A., Wrenn, R.F., and Frieden, C. 1983. Analysis of Numerical Methods for Computer Simulation of Kinetic Processes: Development of KINSIM - A Flexible, Portable System. Anal. Biochem., 130, 134–145.PubMedCrossRefGoogle Scholar
  6. 6.
    Pendleton, R.B. 1989. Hydroperoxide Stimulation of Prostaglandin Endoperoxide Synthase. Doctoral Thesis, University of Illinois, Urbana-Champaign.Google Scholar
  7. 7.
    Lands, W.E.M. and Pendleton, R.B. 1989. n-3 Fatty Acids and Hydroperoxide Activation of Fatty Acid Oxygenases. In: Oxygen Radicals in Biology and Medicine (Simic, Ward, and Taylor, eds.). Plenum Pub. Corp., pp 675–681.Google Scholar

Copyright information

© Springer Science+Business Media New York 1991

Authors and Affiliations

  • R. B. Pendleton
    • 1
  • W. E. M. Lands
    • 1
  1. 1.Department of Biological ChemistryUniversity of Illinois at ChicagoChicagoUSA

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