Molecular basis for differential elongation of omega-3 docosapentaenoic acid by the rat Elovl5 and Elovl2[S]
Functional characterization of the rat elongases, Elovl5 and Elovl2, has identified that Elovl2 is crucial for omega-3 docosahexaenoic acid (DHA) (22:6n-3) synthesis. While the substrate specificities of the rat elongases had some overlap, only Elovl2 can convert the C22 omega-3 PUFA docosapentaenoi...
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| Format: | Article |
| Language: | English |
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Elsevier
2013-10-01
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| Series: | Journal of Lipid Research |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520353104 |
| _version_ | 1831592255724453888 |
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| author | Melissa K. Gregory Leslie G. Cleland Michael J. James |
| author_facet | Melissa K. Gregory Leslie G. Cleland Michael J. James |
| author_sort | Melissa K. Gregory |
| collection | DOAJ |
| description | Functional characterization of the rat elongases, Elovl5 and Elovl2, has identified that Elovl2 is crucial for omega-3 docosahexaenoic acid (DHA) (22:6n-3) synthesis. While the substrate specificities of the rat elongases had some overlap, only Elovl2 can convert the C22 omega-3 PUFA docosapentaenoic acid (DPA) (22:5n-3) to 24:5n-3, which is the penultimate precursor of DHA. In order to better understand the potential for these elongases to be involved in DHA synthesis, we have examined the molecular reasons for the differences between Elovl5 and Elovl2 in their ability to elongate DPA to 24:5n-3. We identified a region of heterogeneity between Elovl5 and Elovl2 spanning transmembrane domains 6 and 7. Using a yeast expression system, we examined a series of Elovl2/Elovl5 chimeras and point mutations to identify Elovl2 residues within this region which are responsible for DPA substrate specificity. The results indicate that the cysteine at position 217 in Elovl2 and a tryptophan at the equivalent position in Elovl5 explain their differing abilities to elongate DPA to 24:5n-3. Further studies confirmed that Elovl2 C217 is a critical residue for elongation of DPA at the level observed in the native protein. Understanding the ability of elongases to synthesize 24:5n-3 may provide a basis for using sequence data to predict their ability to ultimately support DHA synthesis. |
| first_indexed | 2024-12-18T01:40:16Z |
| format | Article |
| id | doaj.art-98396293d5d840b29daaabe191885122 |
| institution | Directory Open Access Journal |
| issn | 0022-2275 |
| language | English |
| last_indexed | 2024-12-18T01:40:16Z |
| publishDate | 2013-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Journal of Lipid Research |
| spelling | doaj.art-98396293d5d840b29daaabe1918851222022-12-21T21:25:21ZengElsevierJournal of Lipid Research0022-22752013-10-01541028512857Molecular basis for differential elongation of omega-3 docosapentaenoic acid by the rat Elovl5 and Elovl2[S]Melissa K. Gregory0Leslie G. Cleland1Michael J. James2To whom correspondence should be addressed; To whom correspondence should be addressed; Rheumatology Unit, Royal Adelaide Hospital, SA, AustraliaRheumatology Unit, Royal Adelaide Hospital, SA, AustraliaRheumatology Unit, Royal Adelaide Hospital, SA, AustraliaFunctional characterization of the rat elongases, Elovl5 and Elovl2, has identified that Elovl2 is crucial for omega-3 docosahexaenoic acid (DHA) (22:6n-3) synthesis. While the substrate specificities of the rat elongases had some overlap, only Elovl2 can convert the C22 omega-3 PUFA docosapentaenoic acid (DPA) (22:5n-3) to 24:5n-3, which is the penultimate precursor of DHA. In order to better understand the potential for these elongases to be involved in DHA synthesis, we have examined the molecular reasons for the differences between Elovl5 and Elovl2 in their ability to elongate DPA to 24:5n-3. We identified a region of heterogeneity between Elovl5 and Elovl2 spanning transmembrane domains 6 and 7. Using a yeast expression system, we examined a series of Elovl2/Elovl5 chimeras and point mutations to identify Elovl2 residues within this region which are responsible for DPA substrate specificity. The results indicate that the cysteine at position 217 in Elovl2 and a tryptophan at the equivalent position in Elovl5 explain their differing abilities to elongate DPA to 24:5n-3. Further studies confirmed that Elovl2 C217 is a critical residue for elongation of DPA at the level observed in the native protein. Understanding the ability of elongases to synthesize 24:5n-3 may provide a basis for using sequence data to predict their ability to ultimately support DHA synthesis.http://www.sciencedirect.com/science/article/pii/S0022227520353104chimeradesaturasedocosahexaenoic acideicosapentaenoic acidelongase |
| spellingShingle | Melissa K. Gregory Leslie G. Cleland Michael J. James Molecular basis for differential elongation of omega-3 docosapentaenoic acid by the rat Elovl5 and Elovl2[S] Journal of Lipid Research chimera desaturase docosahexaenoic acid eicosapentaenoic acid elongase |
| title | Molecular basis for differential elongation of omega-3 docosapentaenoic acid by the rat Elovl5 and Elovl2[S] |
| title_full | Molecular basis for differential elongation of omega-3 docosapentaenoic acid by the rat Elovl5 and Elovl2[S] |
| title_fullStr | Molecular basis for differential elongation of omega-3 docosapentaenoic acid by the rat Elovl5 and Elovl2[S] |
| title_full_unstemmed | Molecular basis for differential elongation of omega-3 docosapentaenoic acid by the rat Elovl5 and Elovl2[S] |
| title_short | Molecular basis for differential elongation of omega-3 docosapentaenoic acid by the rat Elovl5 and Elovl2[S] |
| title_sort | molecular basis for differential elongation of omega 3 docosapentaenoic acid by the rat elovl5 and elovl2 s |
| topic | chimera desaturase docosahexaenoic acid eicosapentaenoic acid elongase |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520353104 |
| work_keys_str_mv | AT melissakgregory molecularbasisfordifferentialelongationofomega3docosapentaenoicacidbytheratelovl5andelovl2s AT lesliegcleland molecularbasisfordifferentialelongationofomega3docosapentaenoicacidbytheratelovl5andelovl2s AT michaeljjames molecularbasisfordifferentialelongationofomega3docosapentaenoicacidbytheratelovl5andelovl2s |