Geometric and positional fatty acid isomers interact differently with desaturation and elongation of linoleic and linolenic acids in cultured glioma cells

Abstract

A range of geometrical and positional isomers of 18-carbon acyl chains are potential components of diets containing fats from processed vegetable oils or ruminant animals. We have examined seventeen 18-carbon fatty acids, with cis or trans double bonds in positions 8–15, for their effects on desaturation and chain elongation of [1-14C]18:2(n − 6) or [1-14C]18:3(n − 3), primarily to 20:4(n − 6) or 20:5(n − 3) respectively, in cultured glioma cells. All trans monoenoic positional isomers inhibited Δ5 desaturation by approximately 60% when 18:2(n − 6) was the substrate, with no positional discrimination evident; with 18:3(n − 3) as substrate, only the 11- and 12-trans isomers were effective inhibitors of formation of 20:5(n − 3). All cis positional monoene isomers, except for 12-cis 18:1, produced 25–30% inhibition of conversion of 18:2(n − 6) to 20:4(n − 6), but had little effect on the conversion of 18:3(n − 3) to 20:5(n − 3). For dienoic isomers, the presence of a 12-trans bond inhibited formation of both 20:4(n − 6) and 20:5(n − 3) and this was enhanced markedly when the other bond in the dienoic acid was 9-trans. Presence of a 9-trans or 15-trans bond with 12-cis gave little effect except for a slight inhibition of 20:4(n − 6) formation by the 12-cis,15-trans 18:2 isomer. All-cis 20:3(n − 9) blocked Δ5 desaturation, increasing 20:3(n − 6) accumulation from 18:2(n − 6) and suggesting that formation of 20:3(n − 9) from 18:1(n − 9) during essential fatty acid deficiency may further exacerbate the already compromised formation of 20:4(n − 6). Further, the differential effects of various cis and trans isomers on the metabolism of 18:2(n − 6) and 18:3(n − 3) suggest that either Δ5 desaturation is not common in both pathways of conversion of 18:2(n − 6) or 18:3(n − 3) to their primary products or that selective interactions of trans and cis isomers occur when the essential fatty acid substrates are different.Key words: trans isomers, essential fatty acids, desaturation, glioma cells, fatty acid metabolism.