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Vertebrate fatty acyl desaturase with Δ4 activity.
Proc Natl Acad Sci U S A 2010; 107(39):16840-5PN

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 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 DHA synthesis reportedly requires two further elongations, a second Δ6 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 Δ6/Δ5 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 Δ4 Fad activity. This is a unique report of a Fad with Δ4 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 Δ4 desaturation, as well as the more complicated pathway as described above.

Authors+Show Affiliations

Guangdong Provincial Key Laboratory of Marine Biology, Shantou University, Shantou, Guangdong 515063, China. yyli@stu.edu.cnNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20826444

Citation

Li, Yuanyou, et al. "Vertebrate Fatty Acyl Desaturase With Δ4 Activity." Proceedings of the National Academy of Sciences of the United States of America, vol. 107, no. 39, 2010, pp. 16840-5.
Li Y, Monroig O, Zhang L, et al. Vertebrate fatty acyl desaturase with Δ4 activity. Proc Natl Acad Sci USA. 2010;107(39):16840-5.
Li, Y., Monroig, O., Zhang, L., Wang, S., Zheng, X., Dick, J. R., ... Tocher, D. R. (2010). Vertebrate fatty acyl desaturase with Δ4 activity. Proceedings of the National Academy of Sciences of the United States of America, 107(39), pp. 16840-5. doi:10.1073/pnas.1008429107.
Li Y, et al. Vertebrate Fatty Acyl Desaturase With Δ4 Activity. Proc Natl Acad Sci USA. 2010 Sep 28;107(39):16840-5. PubMed PMID: 20826444.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vertebrate fatty acyl desaturase with Δ4 activity. AU - Li,Yuanyou, AU - Monroig,Oscar, AU - Zhang,Liang, AU - Wang,Shuqi, AU - Zheng,Xiaozhong, AU - Dick,James R, AU - You,Cuihong, AU - Tocher,Douglas R, Y1 - 2010/09/08/ PY - 2010/9/10/entrez PY - 2010/9/10/pubmed PY - 2010/10/29/medline SP - 16840 EP - 5 JF - Proceedings of the National Academy of Sciences of the United States of America JO - Proc. Natl. Acad. Sci. U.S.A. VL - 107 IS - 39 N2 - 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 DHA synthesis reportedly requires two further elongations, a second Δ6 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 Δ6/Δ5 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 Δ4 Fad activity. This is a unique report of a Fad with Δ4 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 Δ4 desaturation, as well as the more complicated pathway as described above. SN - 1091-6490 UR - https://www.unboundmedicine.com/medline/citation/20826444/Vertebrate_fatty_acyl_desaturase_with_Δ4_activity_ L2 - http://www.pnas.org/cgi/pmidlookup?view=long&pmid=20826444 DB - PRIME DP - Unbound Medicine ER -