Biosynthetic pathway of ω3 and ω6 polyunsaturated fatty acids (PUFAs)

Biosynthetic pathway of ω3 and ω6 polyunsaturated fatty acids (PUFAs). Fatty acids are obtained from the diet or by de novo FA synthesis (upper left), which builds saturated fatty acids (SFA) by 2-carbon unit increments to the 18-carbon stearic acid (C18:0; i.e., 18 carbons with no double bonds) and takes place in all organisms. Stearoyl coenzyme A desaturase 1(SCD1) initiates fatty acid desaturation and generates the precursors of the ω-7 and ω-9 series fatty acids (upper left). The lack of Δ-12 and Δ-15 desaturase (dashed box) in animals renders linoleic acid (LA) and α-linolenic acid (ALA) essential fatty acids (**) and thus must be obtained from the diet, generally from plant-derived sources. The synthesis of ω-9 (derived from oleic acid, 18:1ω9; series not shown), ω-6 (from LA, 18:2ω6) and ω-3 (from ALA, 18:3ω) PUFAs proceeds in parallel, with the activity of Δ-6 desaturase (FADS2) thought to be the rate-limiting step in PUFA synthesis. In animals and organisms at the base of the food chain, LC-PUFAs are synthesized by alternating actions of elongases (red arrows) and desaturases (blue arrows). In mammals, a variety of enzymes (green arrows) generate numerous bioactive derivatives from ω-6 (DHGLA and AA) and ω-3 (EPA, DHA) PUFAs that have numerous targets and functions throughout the body. With the exception of the series-1 prostaglandins (PG), thromboxanes (TX), and leukotrienes (LT) derived from DHGLA, the ω6-derived lipid mediators (series-2 and -4) tend to have proinflammatory actions. Like the series-1 lipid mediators, the series-3 and -5 metabolites of ω3 PUFAs generally exhibit less inflammatory to anti-inflammatory properties. AA, arachidonic acid; DHGLA, dihomo-gamma-linolenic acid; EPA, eicosapentanoic acid; FADS, fatty acid desaturase.

Publication

FADS genetic variants and ω-6 polyunsaturated fatty acid metabolism in a homogeneous island population. (2010) Rasika A. Mathias, et al. J Lipid Res. 2010 Sep;51(9):2766-2774. Figure: F1. All organisms Drosophila melanogaster Homo sapiens

Disease mentions