INHIBITION OF PROSTAGLANDIN BIOSYNTHESIS BY EICOSAPENTAENOIC ACID

Eicosapentaenoic acid [20:5(n-3)] is not oxidized by the purified cyclooxygenase from sheep vesicular glands in the conditions of low peroxide tone in which arachidonate [20:4(n-6)] is rapidly oxygenated. When the level of peroxide in incubation mixtures is allowed to rise, there is a dramatic change in reactivity of the cyclooxygenase to react with 20:5(n-3) at one-half the rate and one-third the extent observed with 20:4(n-6). Overall, the low peroxide levels expected in vivo would most probably cause the (n-3) type of fatty acid to be a general inhibitor of prostaglandin formation, through both reversible and irreversible actions at the enzyme site. © 1979.