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Dual functions of the trans-2-enoyl-CoA reductase TER in the sphingosine 1-phosphate metabolic pathway and in fatty acid elongation.
J Biol Chem 2014; 289(36):24736-48JB

Abstract

The sphingolipid metabolite sphingosine 1-phosphate (S1P) functions as a lipid mediator and as a key intermediate of the sole sphingolipid to glycerophospholipid metabolic pathway (S1P metabolic pathway). In this pathway, S1P is converted to palmitoyl-CoA through 4 reactions, then incorporated mainly into glycerophospholipids. Although most of the genes responsible for the S1P metabolic pathway have been identified, the gene encoding the trans-2-enoyl-CoA reductase, responsible for the saturation step (conversion of trans-2-hexadecenoyl-CoA to palmitoyl-CoA) remains unidentified. In the present study, we show that TER is the missing gene in mammals using analyses involving yeast cells, deleting the TER homolog TSC13, and TER-knockdown HeLa cells. TER is known to be involved in the production of very long-chain fatty acids (VLCFAs). A significant proportion of the saturated and monounsaturated VLCFAs are used for sphingolipid synthesis. Therefore, TER is involved in both the production of VLCFAs used in the fatty acid moiety of sphingolipids as well as in the degradation of the sphingosine moiety of sphingolipids via S1P.

Authors+Show Affiliations

From the Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-chome, Kita-ku, Sapporo 060-0812, Japan.From the Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-chome, Kita-ku, Sapporo 060-0812, Japan.From the Laboratory of Biochemistry, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-chome, Kita-ku, Sapporo 060-0812, Japan kihara@pharm.hokudai.ac.jp.

Pub Type(s)

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

Language

eng

PubMed ID

25049234

Citation

Wakashima, Takeshi, et al. "Dual Functions of the trans-2-enoyl-CoA Reductase TER in the Sphingosine 1-phosphate Metabolic Pathway and in Fatty Acid Elongation." The Journal of Biological Chemistry, vol. 289, no. 36, 2014, pp. 24736-48.
Wakashima T, Abe K, Kihara A. Dual functions of the trans-2-enoyl-CoA reductase TER in the sphingosine 1-phosphate metabolic pathway and in fatty acid elongation. J Biol Chem. 2014;289(36):24736-48.
Wakashima, T., Abe, K., & Kihara, A. (2014). Dual functions of the trans-2-enoyl-CoA reductase TER in the sphingosine 1-phosphate metabolic pathway and in fatty acid elongation. The Journal of Biological Chemistry, 289(36), pp. 24736-48. doi:10.1074/jbc.M114.571869.
Wakashima T, Abe K, Kihara A. Dual Functions of the trans-2-enoyl-CoA Reductase TER in the Sphingosine 1-phosphate Metabolic Pathway and in Fatty Acid Elongation. J Biol Chem. 2014 Sep 5;289(36):24736-48. PubMed PMID: 25049234.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Dual functions of the trans-2-enoyl-CoA reductase TER in the sphingosine 1-phosphate metabolic pathway and in fatty acid elongation. AU - Wakashima,Takeshi, AU - Abe,Kensuke, AU - Kihara,Akio, Y1 - 2014/07/21/ PY - 2014/7/23/entrez PY - 2014/7/23/pubmed PY - 2015/1/30/medline KW - Fatty Acid KW - Lipid KW - Lipid Metabolism KW - Lysophospholipid KW - Phospholipid KW - Sphingolipid KW - Sphingosine 1-Phosphate (S1P) KW - Very Long-chain Fatty Acid KW - Yeast SP - 24736 EP - 48 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 289 IS - 36 N2 - The sphingolipid metabolite sphingosine 1-phosphate (S1P) functions as a lipid mediator and as a key intermediate of the sole sphingolipid to glycerophospholipid metabolic pathway (S1P metabolic pathway). In this pathway, S1P is converted to palmitoyl-CoA through 4 reactions, then incorporated mainly into glycerophospholipids. Although most of the genes responsible for the S1P metabolic pathway have been identified, the gene encoding the trans-2-enoyl-CoA reductase, responsible for the saturation step (conversion of trans-2-hexadecenoyl-CoA to palmitoyl-CoA) remains unidentified. In the present study, we show that TER is the missing gene in mammals using analyses involving yeast cells, deleting the TER homolog TSC13, and TER-knockdown HeLa cells. TER is known to be involved in the production of very long-chain fatty acids (VLCFAs). A significant proportion of the saturated and monounsaturated VLCFAs are used for sphingolipid synthesis. Therefore, TER is involved in both the production of VLCFAs used in the fatty acid moiety of sphingolipids as well as in the degradation of the sphingosine moiety of sphingolipids via S1P. SN - 1083-351X UR - https://www.unboundmedicine.com/medline/citation/25049234/Dual_functions_of_the_trans_2_enoyl_CoA_reductase_TER_in_the_sphingosine_1_phosphate_metabolic_pathway_and_in_fatty_acid_elongation_ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=25049234 DB - PRIME DP - Unbound Medicine ER -