Omega-6 fatty acid metabolic pathway enzymes (FADS/ELOVL pathway)

The omega-6 fatty acid metabolic pathway enzymes, primarily including Fatty acid desaturase 2 (FADS2), Elongation of very long chain fatty acids protein 5 (ELOVL5), and Fatty acid desaturase 1 (FADS1), regulate the conversion of dietary linoleic acid into long-chain polyunsaturated fatty acids [PubMed: 22127335]. Gamma-linolenic acid (GLA) is a key intermediate in this pathway, serving as the direct substrate for ELOVL5, which elongates it to dihomo-gamma-linolenic acid (DGLA) [UniProt: Q9NYP7]. DGLA is a critical metabolic junction; it can be esterified into membrane phospholipids or converted by cyclooxygenases into anti-inflammatory series-1 prostaglandins, such as PGE1 [PubMed: 17168669]. However, DGLA can also be desaturated by FADS1 to form arachidonic acid, the precursor for pro-inflammatory series-2 prostaglandins and series-4 leukotrienes [UniProt: O60427]. Pharmacological or nutritional intervention targeting this pathway, such as GLA supplementation, aims to bypass the rate-limiting Delta-6 desaturase step and favor the production of anti-inflammatory mediators over pro-inflammatory ones [PubMed: 10617991]. This pathway is a significant therapeutic focus for chronic inflammatory diseases, including rheumatoid arthritis and atopic dermatitis, where the balance of fatty acid metabolites is often disrupted [PubMed: 18408140].

Other names

Gamma-linolenic acid metabolic pathwayGLA-DGLA-AA axisDelta-5 and Delta-6 desaturase pathwayOmega-6 desaturation and elongation pathway

Modulation of polyunsaturated fatty acid metabolism to shift the production of eicosanoids from pro-inflammatory to anti-inflammatory profiles.