Fatty acid desaturases and elongases in eicosapentaenoic acid biosynthesis (FADS/ELOVL pathway)

The fatty acid desaturases and elongases in eicosapentaenoic acid (EPA) biosynthesis represent a multi-enzyme pathway responsible for the conversion of the essential omega-3 fatty acid alpha-linolenic acid (ALA) into long-chain polyunsaturated fatty acids (LC-PUFAs) like EPA. This pathway primarily involves Delta-6 desaturase (FADS2), which performs the rate-limiting first step, followed by Fatty acid elongase 5 (ELOVL5) and Delta-5 desaturase (FADS1) (Nakamura & Nara, 2004, PubMed: 15159230). These enzymes are critical for maintaining cellular membrane integrity and producing precursors for anti-inflammatory eicosanoids, such as series-3 prostaglandins and resolvins (Park et al., 2009, PubMed: 19464301). Dysregulation of this pathway is associated with various pathologies, including cardiovascular disease, metabolic syndrome, and certain types of cancer where altered lipid metabolism supports tumor growth. Therapeutic strategies often focus on inhibiting specific enzymes like FADS1 or FADS2 to modulate the balance between pro-inflammatory omega-6 and anti-inflammatory omega-3 metabolites (UniProt: O95864, P59155). Genetic polymorphisms in the FADS gene cluster significantly influence individual EPA levels and are used as biomarkers for metabolic health and dietary requirements. Targeting this pathway offers a way to influence the systemic inflammatory environment by shifting the lipidome toward a more pro-resolving state, though complete inhibition may lead to safety concerns such as essential fatty acid deficiency.

Other names

FADS/ELOVL pathwayOmega-3 fatty acid biosynthetic pathwayDelta-5/Delta-6 desaturase systemPUFA biosynthetic pathway

Inhibition of desaturation or elongation steps to modulate the ratio of omega-3 to omega-6 fatty acids and their downstream eicosanoid metabolites.