1. Dual functions of the trans-2-enoyl-CoA reductase TER in the sphingosine 1-phosphate metabolic pathway and in fatty acid elongation
- Author
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Akio Kihara, Kensuke Abe, and Takeshi Wakashima
- Subjects
Oxidoreductases Acting on CH-CH Group Donors ,Saccharomyces cerevisiae Proteins ,Very long chain fatty acid ,Saccharomyces cerevisiae ,Biology ,Biochemistry ,PC12 Cells ,Gene Expression Regulation, Enzymologic ,chemistry.chemical_compound ,Sphingosine ,Animals ,Humans ,Sphingosine-1-phosphate ,Molecular Biology ,Aldehyde-Lyases ,chemistry.chemical_classification ,Sphingolipids ,Reverse Transcriptase Polymerase Chain Reaction ,Fatty Acids ,Fatty acid ,Cell Biology ,Lipid signaling ,Hep G2 Cells ,Sphingolipid ,Lipids ,Rats ,Metabolic pathway ,Phosphotransferases (Alcohol Group Acceptor) ,chemistry ,Mutation ,Fatty acid elongation ,lipids (amino acids, peptides, and proteins) ,RNA Interference ,Lysophospholipids ,Metabolic Networks and Pathways ,HeLa Cells - 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.
- Published
- 2014