Arachidonic (20:4(n-6)), eicosapentaenoic (20:5(n-3)), and docosahexaenoic (22:6(n-3)) acids are major components of brain and retina phospholipids, substrates for eicosanoid production, and regulators of nuclear transcription factors. One of the two rate-limiting steps in the production of these polyenoic fatty acids is the desaturation of 20:3(n-6) and 20:4(n-3) by Δ-5 desaturase. This report describes the cloning and expression of the human Δ-5 desaturase, and it compares the structural characteristics and nutritional regulation of the Δ-5 and Δ-6 desaturases. The open reading frame of the human Δ-5 desaturase encodes a 444-amino acid peptide which is identical in size to the Δ-6 desaturase and which shares 61% identity with the human Δ-6 desaturase. The Δ-5 desaturase contains two membrane-spanning domains, three histidine-rich regions, and a cytochrome b5 domain that all align perfectly with the same domains located in the Δ-6 desaturase. Expression of the open reading frame in Chinese hamster ovary cells instilled the ability to convert 20:3(n-6) to 20:4(n-6). Northern analysis revealed that many human tissues including skeletal muscle, lung, placenta, kidney, and pancreas expressed Δ-5 desaturase mRNA, but Δ-5 desaturase was most abundant in the liver, brain, and heart. However, in all tissues, the abundance of Δ-5 desaturase mRNA was much lower than that observed for the Δ-6 desaturase. When rats were fed a diet containing 10% safflower oil or menhaden fish oil, the level of hepatic mRNA for Δ-5 and Δ-6 desaturase was only 25% of that found in the liver of rats fed a fat-free diet or a diet containing triolein. Finally, a BLAST and Genemap search of the human genome revealed that the Δ-5 and Δ-6 desaturase genes reside in reverse orientation on chromosome 11 and that they are separated by <11,000 base pairs.
This work was supported by the National Institutes of Health Grant DK 53872 and by the sponsors of the M. M. Love Chair in Nutritional, Cellular, and Molecular Sciences at the University of Texas-Austin (to S. D. C.).The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
