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Identification of acyl-CoA synthetases involved in the mammalian sphingosine 1-phosphate metabolic pathway

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Title: Identification of acyl-CoA synthetases involved in the mammalian sphingosine 1-phosphate metabolic pathway
Authors: Ohkuni, Aya Browse this author
Ohno, Yusuke Browse this author
Kihara, Akio Browse this author →KAKEN DB
Keywords: Acyl-CoA synthetase
Sphingosine 1-phosphate
Issue Date: 13-Dec-2013
Publisher: Academic press inc elsevier science
Journal Title: Biochemical and biophysical research communications
Volume: 442
Issue: 3-4
Start Page: 195
End Page: 201
Publisher DOI: 10.1016/j.bbrc.2013.11.036
PMID: 24269233
Abstract: Sphingosine 1-phosphate (SIP) plays important roles both as a bioactive lipid molecule and an intermediate of the sphingolipid-to-glycerophospholipid metabolic pathway. To identify human acyl-CoA synthetases (ACSs) involved in SIP metabolism, we cloned all 26 human ACS genes and examined their abilities to restore deficient sphingolipid-to-glycerophospholipid metabolism in a yeast mutant lacking two ACS genes, FAA1 and FAA4. Here, in addition to the previously identified ACSL family members (ACSL1, 3, 4, 5, and 6), we found that ACSVL1, ACSVL4, and ACSBG1 also restored metabolism. All 8 ACSs were localized either exclusively or partly to the endoplasmic reticulum (ER), where SIP metabolism takes place. We previously proposed the entire SIP metabolic pathway from results obtained using yeast cells, i.e., SIP is metabolized to glycerophospholipids via trans-2-hexadecenal, trans-2-hexadecenoic acid, trans-2-hexadecenoyl-CoA, and palmitoyl-CoA. However, as SIP is not a naturally occurring long-chain base 1-phosphate in yeast, the validity of this pathway required further verification using mammalian cells. In the present study, we treated HeLa cells with the ACS inhibitor triacsin C and found that inhibition of ACSs resulted in accumulation of trans-2-hexadecenoic acid as in ACS mutant yeast. From these results, we conclude that SIP is metabolized by a common pathway in eukaryotes. (C) 2013 Elsevier Inc. All rights reserved.
Type: article (author version)
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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