Abstract
In mammals, polyunsaturated fatty acids (PUFAs) such as linoleic acid (18:2n-6) and α -linolenic acid (18:3n-3) cannot be synthesized de novo. Therefore, these PUFAs are essential fatty acids (EFAs). However, these PUFAs can be converted to arachidonic acid (20:4n-6) and eicosapentaenoic acid (20:5n-3). Mead acid (20:3n-9), is an unusual n-9 series PUFA, which is endogenously synthesized from oleic acid (18:1n-9) in an essential fatty acid (EFA)-deficiency state. In this study, we showed that Mead acid was produced from oleic acid by two desaturation enzymes (FADS1 and FADS2) and one elongation enzyme (ELOVL5), indicating that n-3, n-6, and n-9 PUFAs are metabolized by the same enzymes. Furthermore, ELOVL5 acquired an elongation activity towards oleic acid under EFA-deficient state, which allows it to synthesize Mead acid. We revealed a novel regulatory mechanism that the substrate preference of ELOVL5 was modified by a post-translational modification.
The function of Mead acid during EFA-deficiency is not known, but we showed that the inhibition of Mead acid synthesis induced hepatic triacylglycerol accumulation via the suppression of very low-density lipoprotein (VLDL) secretion in EFA-deficiency mice. From these results, it is possible that Mead acid functions as a substitute for the PUFA produced from EFAs in VLDL secretion during EFA-deficiency.
