Curcumin (1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione) inhibited noncompetitively rat liver microsomal delta 5 desaturase (Ki = 36 microM) and delta 6 desaturase (Ki = 28 microM). Although curcumin has a symmetrical structure with a methylene group as the center, only half the structure is essential for the desaturase inhibition. The structure necessary for the inhibition is similar to that of alkyl gallate (H. Kawashima et al., Biochim. Biophys. Acta, in press), i.e., a 3-hydroxy group of the aromatic ring is essential for the inhibition and a free carboxyl group at the end opposite to the aromatic ring interferes with the inhibitory effect. The following structural features of curcumin are necessary for the desaturase inhibition: (i) the aromatic ring conjugated with the double bond between the 1 and 2 (or 6 and 7) positions; (ii) both 4-hydroxy and 3-methoxy groups (for both desaturase inhibitions); and (iii) only a 4-hydroxy group (for delta 6 desaturase inhibition).