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

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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.

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詳細情報 詳細情報について

  • CRID
    1050282813992341376
  • NII論文ID
    120005385315
  • HANDLE
    2115/54775
  • ISSN
    0006291X
  • 本文言語コード
    en
  • 資料種別
    journal article
  • データソース種別
    • IRDB
    • CiNii Articles

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