Figure 4. Overview of metabolites identified in the premutation in the context of the biosynthesis of fatty acids and eicosanoids.
Different fatty acid ratios were used to estimate enzymatic activities of steps involved in fatty acid desaturation, elongation and de novo lipogenesis. The ratio of arachidonic to linoleic acid ratio (C20:4 n-6/C18:2 n-6) was evaluated as an index of the activation of the pathway leading to the formation of prostaglandins of the 2 series starting from linoleic acid, via the formation of arachidonic acid. An increased pro-inflammatory status in carriers was inferred from the lower ratio of fatty acids of the n-3 series over that of the n-6 series, as prostaglandins generated via the Δ5–6 desaturase pathway are more pro-inflammatory than those originated from alpha-linolenic acid which generates prostaglandins of the 3 series (thick red arrows vs. thin green arrows). Boxed metabolites were identified by metabolomics. Black, thick arrows are based on the abundance indicated under Table 2. Abbreviations: ALA, alpha-linolenic acid; LA, linoleic acid; EPA, eicosapentaenoic acid; DPA, docosapentaenoic acid; DHA, docosahexaenoic acid; AA, arachidonic acid; DHGLA, dihomo-gamma-linolenic acid; MUFAs, monounsaturated fatty acids; PUFAS, polyunsaturated fatty acids; SFAs, saturated fatty acids; E, elongase; desaturases are indicated as delta followed by the bond affected; OX, peroxisomal beta-oxidation. Eicosanoids with anti-inflammatory properties (resolvins, protectins) are indicated with thin green arrows whereas pro-inflammatory (prostanglandins of the series 2 and LTB4) are indicated with thick red arrows.