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ELOVL4 protein preferentially elongates 20:5n3 to very long chain polyunsaturated fatty acids over 20:4n6 and 22:6n3.
MedLine Citation:
PMID:  22158834     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
We hypothesized that reduction/loss of very long chain polyunsaturated fatty acids (VLC-PUFA) due to mutations in the Elongation of Very Long Chain Fatty Acids-4 (ELOVL4) protein contributes to retinal degeneration in autosomal dominant Stargardt macular dystrophy (STGD3) and age-related macular degeneration; hence, increasing VLC-PUFA in the retina of these patients could provide some therapeutic benefits. Thus, we tested the efficiency of elongation of C20-C22 PUFA by the ELOVL4 protein to determine which substrates are the best precursors for biosynthesis of VLC-PUFA. The ELOVL4 protein was expressed in pheochromocytoma cells, while GFP-expressing and non-transduced cells served as controls. The cells were treated with 20:5n3, 22:6n3 and 20:4n6, either individually or in equal combinations. Both transduced and control cells internalized and elongated the supplemented fatty acids to C22-C26 precursors. Only ELOVL4-expressing cells synthesized C28-C38 VLC-PUFA from these precursors. In general, 20:5n3 was more efficiently elongated to VLC-PUFA, regardless of whether it was in combination with 22:6n3 or with 20:4n6 in the ELOVL4-expressing cells. In each fatty acid treatment group, C34 and C36 VLC-PUFA were the predominant VLC-PUFA in the ELOVL4-expressing cells. In summary, 20:5n3, followed by 20:4n6 seems to be the best precursor for boosting the synthesis of VLC-PUFA by ELOVL4 protein.
Authors:
Man Yu; Aaron F Benham; Sreemathi Logan; R Steven Brush; Md Nawajes A Mandal; Robert E Anderson; Martin-Paul Agbaga
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-12-9
Journal Detail:
Title:  Journal of lipid research     Volume:  -     ISSN:  0022-2275     ISO Abbreviation:  -     Publication Date:  2011 Dec 
Date Detail:
Created Date:  2011-12-13     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
West China Hospital, Sichuan University, China;
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