Conversion of alpha linolenic acid to longer chain n3 fatty acids: competition with linoleic and oleic acids for the delta 6 desaturase

The bioavailability of n3 long chain polyunsaturated fatty acids is ensured by their nutritional intake but also by the conversion from their essential fatty acid precursor alpha linolenic acid (ALA). This conversion pathway involves the delta 6 desaturase which also catalyzes linoleic (LA) and oleic (OLA) acid conversion into long chain fatty acids. Because the intakes of LA and OLA are considerably elevated compared to those of ALA in humans, they may create a competition for the delta 6 desaturase. This study aimed at measuring the ability of either LA or
OLA to compete for this first rate limiting step of the n3 conversion pathway. Firstly, we measured the delta6 desaturase activity ex vivo by using radiolabelled ALA and increasing concentrations of LA or OLA. These results demonstrate a strong inhibition (70  percent  compared without ALA) observed for the highest dose 180 nmol for both LA and OLA. Secondly, in vitro conversion of ALA into longer chain fatty acids was assayed in the presence of increasing concentrations of LA or OLA (100600 microM) and constant concentration of ALA
(100 microM) in the incubation media. The gradual increase in LA in the culture medium led to a gradual inhibition of the EPA (C20:5 n3) formation from ALA, and at the highest concentration (600  microM LA) the EPA level was similar to the control condition. This effect does not appear significant with OLA. Thirdly we confirmed these results with an in vivo approach by liver fatty acid analysis of rats fed experimental diets enriched with OLA and/or LA. Altogether, our results have shown that both LA and OLA are two main competitors for ALA conversion
and consequently the availability of LC n3 PUFA. This should be included in nutritional guidelines approaches. (Authors abstract)