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Identification of acyl-CoA synthetases involved in the mammalian sphingosine 1-phosphate metabolic pathway.
Biochem Biophys Res Commun 2013; 442(3-4):195-201BB

Abstract

Sphingosine 1-phosphate (S1P) 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 S1P 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 S1P metabolism takes place. We previously proposed the entire S1P metabolic pathway from results obtained using yeast cells, i.e., S1P is metabolized to glycerophospholipids via trans-2-hexadecenal, trans-2-hexadecenoic acid, trans-2-hexadecenoyl-CoA, and palmitoyl-CoA. However, as S1P 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 S1P is metabolized by a common pathway in eukaryotes.

Authors+Show Affiliations

Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-chome, Kita-ku, Sapporo 060-0812, Japan.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

24269233

Citation

Ohkuni, Aya, et al. "Identification of acyl-CoA Synthetases Involved in the Mammalian Sphingosine 1-phosphate Metabolic Pathway." Biochemical and Biophysical Research Communications, vol. 442, no. 3-4, 2013, pp. 195-201.
Ohkuni A, Ohno Y, Kihara A. Identification of acyl-CoA synthetases involved in the mammalian sphingosine 1-phosphate metabolic pathway. Biochem Biophys Res Commun. 2013;442(3-4):195-201.
Ohkuni, A., Ohno, Y., & Kihara, A. (2013). Identification of acyl-CoA synthetases involved in the mammalian sphingosine 1-phosphate metabolic pathway. Biochemical and Biophysical Research Communications, 442(3-4), pp. 195-201. doi:10.1016/j.bbrc.2013.11.036.
Ohkuni A, Ohno Y, Kihara A. Identification of acyl-CoA Synthetases Involved in the Mammalian Sphingosine 1-phosphate Metabolic Pathway. Biochem Biophys Res Commun. 2013 Dec 13;442(3-4):195-201. PubMed PMID: 24269233.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Identification of acyl-CoA synthetases involved in the mammalian sphingosine 1-phosphate metabolic pathway. AU - Ohkuni,Aya, AU - Ohno,Yusuke, AU - Kihara,Akio, Y1 - 2013/11/19/ PY - 2013/11/06/received PY - 2013/11/09/accepted PY - 2013/11/26/entrez PY - 2013/11/26/pubmed PY - 2014/4/30/medline KW - ACS KW - ACS bubblegum KW - ACS long-chain KW - ACS medium-chain KW - ACS short-chain KW - ACS very long-chain KW - ACSBG KW - ACSL KW - ACSM KW - ACSS KW - ACSVL KW - Acyl-CoA synthetase KW - DHS KW - DHS1P KW - ER KW - FA KW - GAPDH KW - Glycerophospholipid KW - IPC KW - LCB KW - LCB 1-phosphate KW - LCBP KW - LCFA KW - Lipid KW - M(IP)(2)C KW - MIPC KW - PC KW - PE KW - PI KW - PS KW - S1P KW - SC KW - SPH KW - Sphingolipid KW - Sphingosine 1-phosphate KW - VLCFA KW - acyl-CoA synthetase KW - dihydrosphingosine KW - dihydrosphingosine 1-phosphate KW - endoplasmic reticulum KW - fatty acid KW - glyceraldehyde 3-phosphate dehydrogenase KW - inositol phosphorylceramide KW - long-chain base KW - long-chain fatty acid KW - mannosyldiinositol phosphorylceramide KW - mannosylinositol phosphorylceramide KW - phosphatidylcholine KW - phosphatidylethanolamine KW - phosphatidylinositol KW - phosphatidylserine KW - sphingosine KW - sphingosine 1-phosphate KW - synthetic complete KW - very long-chain fatty acid SP - 195 EP - 201 JF - Biochemical and biophysical research communications JO - Biochem. Biophys. Res. Commun. VL - 442 IS - 3-4 N2 - Sphingosine 1-phosphate (S1P) 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 S1P 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 S1P metabolism takes place. We previously proposed the entire S1P metabolic pathway from results obtained using yeast cells, i.e., S1P is metabolized to glycerophospholipids via trans-2-hexadecenal, trans-2-hexadecenoic acid, trans-2-hexadecenoyl-CoA, and palmitoyl-CoA. However, as S1P 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 S1P is metabolized by a common pathway in eukaryotes. SN - 1090-2104 UR - https://www.unboundmedicine.com/medline/citation/24269233/Identification_of_acyl_CoA_synthetases_involved_in_the_mammalian_sphingosine_1_phosphate_metabolic_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-291X(13)01918-9 DB - PRIME DP - Unbound Medicine ER -