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ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis

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Please use this identifier to cite or link to this item:http://hdl.handle.net/2115/45300

Title: ELOVL1 production of C24 acyl-CoAs is linked to C24 sphingolipid synthesis
Authors: Ohno, Yusuke Browse this author
Suto, Shota Browse this author
Yamanaka, Masao Browse this author
Mizutani, Yukiko Browse this author →KAKEN DB
Mitsutake, Susumu Browse this author →KAKEN DB
Igarashi, Yasuyuki Browse this author →KAKEN DB
Sassa, Takayuki Browse this author →KAKEN DB
Kihara, Akio Browse this author →KAKEN DB
Keywords: acyl-CoA
lipid metabolism
monounsaturated fatty acid
polyunsaturated fatty acid
saturated fatty acid
Issue Date: 26-Oct-2010
Publisher: National Academy of Sciences
Journal Title: Proceedings of the National Academy of Sciences of the United States of America
Volume: 107
Issue: 43
Start Page: 18439
End Page: 18444
Publisher DOI: 10.1073/pnas.1005572107
Abstract: Very long-chain fatty acids (VLCFAs) exert a variety of cellular functions and are associated with numerous diseases. However, the precise pathway behind their elongation has remained elusive. Moreover, few regulatory mechanisms for VLCFAs synthesis have been identified. Elongases catalyze the first of four steps in the VLCFA elongation cycle; mammals have seven elongases (ELOVL1-7). In the present study, we determined the precise substrate specificities of all the ELOVLs by in vitro analyses. Particularly notable was the high activity exhibited by ELOVL1 toward saturated and monounsaturated C20- and C22-CoAs, and that it was essential for the production of C24 sphingolipids, which are unique in their capacity to interdigitate within the membrane as a result of their long chain length. We further established that ELOVL1 activity is regulated with the ceramide synthase CERS2, an enzyme essential for C24 sphingolipid synthesis. This regulation may ensure that the production of C24-CoA by elongation is coordinated with its utilization. Finally, knock-down of ELOVL1 caused a reduction in the activity of the Src kinase LYN, confirming that C24-sphingolipids are particularly important in membrane microdomain function.
Type: article (author version)
URI: http://hdl.handle.net/2115/45300
Appears in Collections:薬学研究院 (Faculty of Pharmaceutical Sciences) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 木原 章雄

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