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

Abstract

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].