Kinetic Basis for the Impaired Oxygenation of Eicosapentaenoate by Prostaglandin Endoperoxide Synthase
- 56 Downloads
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 .
KeywordsPolyunsaturated Fatty Acid Kinetic Rate Constant Prostaglandin Biosynthesis Cyclooxygenase Activity Impaired Oxygenation
Unable to display preview. Download preview PDF.
- 1.W.E.M. Lands. 1986. Fish and Human Health. Academic Press, Orlando, FL.Google Scholar
- 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
- 6.Pendleton, R.B. 1989. Hydroperoxide Stimulation of Prostaglandin Endoperoxide Synthase. Doctoral Thesis, University of Illinois, Urbana-Champaign.Google Scholar
- 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