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 (PUFA), the precursor of eicosanoids. Since Δ6-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 Δ6-desaturase. A unique and simple model, i.e., baker's yeast (Saccharomyces cerevisiae) transformed with fungal Δ6-desaturase gene, previously established, was used to investigate the direct effect of CLA on Δ6-desaturase. This model allows LA to be converted to γ-linolenic acid (GLA; 18∶3n−6) but not GLA to its metabolite(s). No metabolites of CLA were found in the lipids of the yeast transformed with Δ6-desaturase. The inability to convert CLA to conjugated GLA 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 Δ6-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 Δ6-desaturase. Since CLA did not cause significant changes in the level of Δ6-desaturase mRNA, the inhibition of GLA production could not be attributed to suppression of Δ6-desaturate gene expression at the transcriptional level.