Structure, Function, and Dietary Regulation of Δ6, Δ5, and Δ9 Desaturases

Abstract

Fatty acid desaturases introduce a double bond in a specific position of long-chain fatty acids, and are conserved across kingdoms. Degree of unsaturation of fatty acids affects physical properties of membrane phospholipids and stored triglycerides. In addition, metabolites of polyunsaturated fatty acids are used as signaling molecules in many organisms. Three desaturases, Delta9, Delta6, and Delta5, are present in humans. Delta-9 catalyzes synthesis of monounsaturated fatty acids. Oleic acid, a main product of Delta9 desaturase, is the major fatty acid in mammalian adipose triglycerides, and is also used for phospholipid and cholesteryl ester synthesis. Delta-6 and Delta5 desaturases are required for the synthesis of highly unsaturated fatty acids (HUFAs), which are mainly esterified into phospholipids and contribute to maintaining membrane fluidity. While HUFAs may be required for cold tolerance in plants and fish, the primary role of HUFAs in mammals is cell signaling. Arachidonic acid is required as substrates for eicosanoid synthesis, while docosahexaenoic acid is required in visual and neuronal functions. Desaturases in mammals are regulated at the transcriptional level. Reflecting overlapping functions, three desaturases share a common mechanism of a feedback regulation to maintain products in membrane phospholipids. At the same time, regulation of Delta9 desaturase differs from Delta6 and Delta5 desaturases because its products are incorporated into more diverse lipid groups. Combinations of multiple transcription factors achieve this sophisticated differential regulation.

Serum phospholipid and cholesteryl ester fatty acids and estimated desaturase activities are related to overweight and cardiovascular risk factors in adolescents

“…3,4,14,19,25,26 A similar pattern was observed in obese children in our study and others, 16,27 although study results have been inconsistent. 18 Desaturase activity Consistent with most previous studies of adults 4,11,14,28 and children, 16,18 we found that the estimated activities of D6 and D9 DAs were positively associated with adiposity and insulin measures in our study of adolescents. Further, D6 DA was also adversely associated with other CVD risk factors, including triglycerides, total cholesterol, LDL-and HDLcholesterol.…”

“…9,10 The composition of fatty acids in the body reflects dietary fat intake and endogenous fatty acid metabolism. 11 Plasma or serum fatty acid composition partly reflects dietary fat intake during the past 2-6 weeks and the fatty acids in body fat tissue represents diet in the past several months or years. 12 Desaturase enzyme activity (modulating fatty acid degree of saturation) 11,13 includes delta (D) 9, D6, and D5 desaturase activities (DAs), the rate-limiting steps for transforming shorter chain fatty acids into longer essential fatty acid metabolites.…”

“…11 Plasma or serum fatty acid composition partly reflects dietary fat intake during the past 2-6 weeks and the fatty acids in body fat tissue represents diet in the past several months or years. 12 Desaturase enzyme activity (modulating fatty acid degree of saturation) 11,13 includes delta (D) 9, D6, and D5 desaturase activities (DAs), the rate-limiting steps for transforming shorter chain fatty acids into longer essential fatty acid metabolites. DAs cannot readily be measured in humans in vivo but can be estimated from relevant product/precursor ratios in plasma or serum.…”

Effects on metabolic markers are modified by PPARG2 and COX2 polymorphisms in infants randomized to fish oil

“…The FADS gene cluster encodes the enzymes D 5 and D 6 desaturase (Marquardt et al 2000;Nakamura and Nara 2004), which are involved in the endogenous synthesis of n-3 LCPUFA (Burdge and Calder 2005). PPARG2 and COX2 encode proteins that play a role in the proposed mechanisms behind the effects of n-3 LCPUFA.…”

Fatty acid desaturases in human adipose tissue: relationships between gene expression, desaturation indexes and insulin resistance

“…Stearoyl-CoA desaturase (SCD) is the key Δ 9 -desaturase in man. The activities of these enzymes produce fatty acids with a greater degree of desaturation, which are required for the efficient synthesis of more complex lipids, such as triacylglycerols [2]. Both animal and human studies suggest that fatty acid desaturases play a role in various metabolic disturbances, such as insulin resistance and dyslipidaemia [3][4][5].…”