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Vertebrate fatty acyl desaturase with ?4 activity.


ABSTRACT: 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 ?6 desaturation of 182n - 6 to produce 183n - 6 that is elongated to 203n - 6 followed by ?5 desaturation. Synthesis of EPA from 183n - 3 requires the same enzymes and pathway as for ARA, but DHA synthesis reportedly requires two further elongations, a second ?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 ?6/?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 225n - 3 to DHA indicating that this S. canaliculatus gene encoded an enzyme having ?4 Fad activity. This is a unique report of a Fad with ?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 225n - 3 followed by ?4 desaturation, as well as the more complicated pathway as described above.

SUBMITTER: Li Y 

PROVIDER: S-EPMC2947896 | biostudies-literature | 2010 Sep

REPOSITORIES: biostudies-literature

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Vertebrate fatty acyl desaturase with Δ4 activity.

Li Yuanyou Y   Monroig Oscar O   Zhang Liang L   Wang Shuqi S   Zheng Xiaozhong X   Dick James R JR   You Cuihong C   Tocher Douglas R DR  

Proceedings of the National Academy of Sciences of the United States of America 20100908 39


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 Δ6 desaturation of 182n - 6 to produce 183n - 6 that is elongated to 203n - 6 followed by Δ5 desaturation. Synthesis of EPA from 183n - 3 requires the same enzymes and pathway as for ARA, but D  ...[more]

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