SESAMIN IS A POTENT AND SPECIFIC INHIBITOR OF DELTA-5 DESATURASE IN POLYUNSATURATED FATTY-ACID BIOSYNTHESIS

Incubation with sesame oil increases the mycelial dihomo-gamma-linolenic acid content of an arachidonic acid-producing fungus, Mortierella alpina, but decreases its arachidonic acid content [Shimizu, S., K. Akimoto, H. Kawashima, Y. Shinmen and H. Yamada (1989) J. Am. Oil Chem. Soc. 66, 237-241]. The factor causing these effects was isolated and identified to be (+)-sesamin. The results obtained in experiments with both a cell-free extract of the fungus and with rat liver microsomes demonstrated that (+)- sesamin specifically inhibits DELTA-5 desaturase at low concentrations, but does not inhibit DELTA-6, DELTA-9 and DELTA-12 desaturases. Kinetic analysis showed that (+)-sesamin is a noncompetitive inhibitor (K(i) for rat liver DELTA-5 desaturase, 155-mu-M). (+)-Sesamolin, (+)-sesaminol and (+)-episesamin also inhibited only DELTA-5 desaturases of the fungus and liver. These results demonstrate that (+)-sesamin and related lignan compounds present in sesame seeds or its oil are specific inhibitors of DELTA-5 desaturase in polyunsaturated fatty acid biosynthesis in both microorganisms and animals.