Effect of conjugated linoleic acid on fungal Δ6-desaturase activity in a transformed yeast system

Conjugated linoleic acid (CLA; 18:2), a group of positional and geometric isomers of linoleic acid (LA; 18:2n-6), has been shown to modulate immune function through its effect on eicosanoid synthesis. This effect has been attributed to a reduced production of n-6 polyunsaturated fatty acid (PU FA), the precursor of eicosanoids. Since Delta6-desaturase is the rate-limiting enzyme of the n-6 PUFA production, it is our hypothesis that CLA, which has similar chemical structure to LA, interacts directly with Delta6-desaturase. A unique and simple model, i.e., baker's yeast (Saccharomyces cerevisiae) transformed with fungal Delta6-desaturase gene, previously established, was used to investigate the direct effect of CLA on Delta6-desaturase. This model allows LA to be converted to gamma -linolenic acid (GLA; 18:3 n-6) but not CLA to its metabolile(s). No metabolites of CLA were found in the lipids of the yeast transformed with Delta6-desaturase. The inability to convert CLA to conjugated CLA was not due to the failure of yeast cells to take up the CLA isomers. CLA mixture and individual isomers significantly inhibited the activity of Delta6-desaturase of the transformed yeast in vivo. Even though its uptake by the yeast was low, CLA c9, t11 isomer was found to be the most potent inhibitor of the four isomers tested, owing to its high inhibitory effect on Delta6-desaturase. Since CLA did not cause significant changes in the level of Delta6-desaturase mRNA, the inhibition of GLA production could not be attributed to suppression of Delta6-desaturase gene expression at the transcriptional level.