期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：39
页码：16840-16845
DOI：10.1073/pnas.1008429107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Biosynthesis of the highly biologically active long-chain polyunsaturated fatty acids, arachidonic (ARA), eicosapentaenoic (EPA), and docosahexaenoic (DHA) acids, in vertebrates requires the introduction of up to three double bonds catalyzed by fatty acyl desaturases (Fad). Synthesis of ARA is achieved by {Delta}6 desaturation of 18:2n - 6 to produce 18:3n - 6 that is elongated to 20:3n - 6 followed by {Delta}5 desaturation. Synthesis of EPA from 18:3n - 3 requires the same enzymes and pathway as for ARA, but DHA synthesis reportedly requires two further elongations, a second {Delta}6 desaturation and a peroxisomal chain shortening step. This paper describes cDNAs, fad1 and fad2, isolated from the herbivorous, marine teleost fish (Siganus canaliculatus) with high similarity to mammalian Fad proteins. Functional characterization of the cDNAs by heterologous expression in the yeast Saccharomyces cerevisiae showed that Fad1 was a bifunctional {Delta}6/{Delta}5 Fad. Previously, functional dual specificity in vertebrates had been demonstrated for a zebrafish Danio rerio Fad and baboon Fad, so the present report suggests bifunctionality may be more widespread in vertebrates. However, Fad2 conferred on the yeast the ability to convert 22:5n - 3 to DHA indicating that this S. canaliculatus gene encoded an enzyme having {Delta}4 Fad activity. This is a unique report of a Fad with {Delta}4 activity in any vertebrate species and indicates that there are two possible mechanisms for DHA biosynthesis, a direct route involving elongation of EPA to 22:5n - 3 followed by {Delta}4 desaturation, as well as the more complicated pathway as described above.
