Δ-6 Desaturase Substrate Competition: Dietary Linoleic Acid (18∶2n-6) Has Only Trivial Effects on α-Linolenic Acid (18∶3n-3) Bioconversion in the Teleost Rainbow Trout

Abstract

It is generally accepted that, in vertebrates, omega-3 (n-3) and omega-6 (n-6) poly-unsaturated fatty acids (PUFA) compete for Δ-6 desaturase enzyme in order to be bioconverted into long-chain PUFA (LC-PUFA). However, recent studies into teleost fatty acid metabolism suggest that these metabolic processes may not conform entirely to what has been previously observed in mammals and other animal models. Recent work on rainbow trout has led us to question specifically if linoleic acid (LA, 18∶2n-6) and α-linolenic acid (ALA, 18∶3n-3) (Δ-6 desaturase substrates) are in direct competition for access to Δ-6 desaturase. Two experimental diets were formulated with fixed levels of ALA, while LA levels were varied (high and low) to examine if increased availability of LA would result in decreased bioconversion of ALA to its LC-PUFA products through substrate competition. No significant difference in ALA metabolism towards n-3 LC-PUFA was exhibited between diets while significant differences were observed in LA metabolism towards n-6 LC-PUFA. These results are evidence for minor if any competition between substrates for Δ-6 desaturase, suggesting that, paradoxically, the activity of Δ-6 desaturase on n-3 and n-6 substrates is independent. These results call for a paradigm shift in the way we approach teleost fatty acid metabolism. The findings are also important with regard to diet formulation in the aquaculture industry as they indicate that there should be no concern for possible substrate competition between 18∶3n-3 and 18∶2n-6, when aiming at increased n-3 LC-PUFA bioconversion in vivo.

Effect of substrate competition in kinetic models of metabolic networks

“…The last case we studied is a pathway, where multiple consecutive reactions are catalysed by the same enzyme. Prominent examples can be found in pathways that process polymers, such as starch and glycogen synthesis and degradation, and fatty acid degradation [19,20,1]. In all these cases, the enzymes accept substrates of different chain lengths, sometimes with increasing or decreasing affinities.…”

Influence of dietary linoleic acid (18:2n-6) and α-linolenic acid (18:3n-3) ratio on fatty acid composition of different tissues in freshwater fish Songpu mirror carp,Cyprinus Carpio

“…; Emery et al . ). Notably, n‐6 HUFA were primarily presented as ARA, and n‐3 HUFA were primarily presented as DHA, suggesting the difference of affinity between n‐6 PUFA and n‐3 PUFA for the desaturase and elongase (Glencross ).…”

“…In general, ARA proportions showed increased trends and DHA showed decreased trends as the increased dietary LA/LNA ratios, the result was consistant with many other studies such as yellow catfish (Tan et al . ), rainbow trout (Emery, Hermon, Hamid, Donald & Turchini ) and grouper (Wu & Chen ), which was possibly because of the variation of LA and LNA as the substrates for elongation and desaturation (Tian et al . ).…”

Maternal Diet Enriched with α-Linolenic or Saturated Fatty Acids Differentially Regulates Gene Expression in the Liver of Mouse Offspring

“…The higher Δ6-desaturase activity on ALA leading to DHA and EPA, in livers of pups born to ALA-fed mothers compared to livers of pups of SFA-fed mothers, may be associated with a direct effect of ALA on the enzyme activity leading, consequently, to a higher production of ω-3 than ω-6 longer products [14] and may be associated with a healthier outcome [5]. These results emerge from very high amounts of dietary ALA. Lower doses should also be tested.…”