Role of Elongase Reactions in LCPUFA Synthesis Figure 6. Examination of product/substrate relationships for desaturation by Fads2. Recombinant S. cerevisiae expressing empty pYES2 vector or Fads2 were grown in the presence of ALA (A) or 24:5n-3 (B). Fatty acids were extracted from the recombinant S. cerevisiae and the amount of each fatty acid was quantified in mg g21 of S. cerevisiae. The results are the means 6 S.D. of triplicate incubations. Values with different symbols are significantly different from each other. doi:10.1371/journal.pone.0029662.g006 conversion, Elovl5 may be more important since our data show it is expressed at much higher levels than Elovl2 in rat liver and heart. However, neither EPA nor DPA elongation were diminished in the liver of Elovl5-/- mice, indicating that Elovl2 was responsible for EPA elongation in these knockout mice [18]. Nevertheless, Elovl2 was upregulated substantially in the Elovl5-/- mice compared with the wild type controls [18]. The serum of Elovl2-/- mice had elevated EPA and DPA levels [19]. However, Elovl5 may have been upregulated in the Elovl2-/- mice resulting in the accumulation of EPA and DPA, analogous to the upregulation of Elovl2 in Elovl5-/- mice, although this was not investigated [19]. Therefore, it remains uncertain if one or both elongases normally contribute to EPA elongation. The scheme in Fig. 8 highlights the essentiality of Elovl2 activity for DHA formation. The finding that 24:5n-3 formation is possibly saturated at substrate concentrations not saturating for DPA formation, provides explanations for previous dietary findings. For example, tracer studies in healthy volunteers showed that increased EPA intake as a fish-based diet, increased the mass of EPA to DPA conversion, but decreased the mass of DPA to 24:5n- 3 conversion [20]. The scheme proposed in Fig. 8 suggests these reported results could be due to increased EPA saturating the second Elovl2 reaction and competing with DPA for Elovl2 activity. The possible saturation of the second Elovl2 reaction provides an explanation for the limitations of both ALA and EPA as progenitors of DHA formation and provides an explanation for the accumulation of DPA when ALA or SDA or EPA is provided in the diet [1,2,3]. SDA enriched soybeans were granted Generally Recognised As Safe (GRAS) status by the US FDA in 2009 (http://www. soymega.com/en/Why-Soymega/). Bypassing the first Fads2 reaction has the potential to improve EPA and DPA tissue levels compared with standard soybean products. However, the present study suggests that Elovl2, both its presence and its activity, will be critical in understanding if DHA synthesis can be increased by dietary means. Given the essentiality of Elovl2 for DHA synthesis, a functional Elovl2 may control the habitat and diet of a range of species such PLoS ONE | www.plosone.org 6 December 2011 | Volume 6 | Issue 12 | e29662