Ceramide phosphoethanolamine synthase

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In enzymology, a ceramide phosphoethanolamine synthase (EC 2.7.8.-) is an enzyme that catalyzes the chemical reaction

a ceramide + a phosphoethanolamine head group donor a ceramide-phosphoethanolamine + side product

Ceramide phosphoethanolamine (CPE) is a sphingolipid consisted of a ceramide and a phosphoethanolamine head group. Thus, this class of enzymes uses ceramide and a donor molecule for phosphoethanolamine as substrates to produce a ceramide phosphoethanolamine and a side product. The head group donor for phosphoethanolamine can be either phosphatidylethanolamine or CDP-ethanolamine, thus the side product is either a 1,2-diacylglycerol or a CMP, respectively.

This enzyme belongs to the family of transferases, specifically those transferring non-standard substituted phosphate groups.

Mammalian Ceramide Phosphoethanolamine Synthases[edit]

In mammalian cells, two CPE synthase activities have been described, one resides in the endoplasmic reticulum, and the other one is associated with the plasma membrane.[1][2][3][4][5] The endoplasmic reticulum-resident CPE synthase, SMSr, is identified as a monofunctional CPE synthase produces trace amounts of CPE.[4][5] On the other hand, mammalian CPE synthase that is on the plasma membrane, SMS2, is a bifunctional enzyme that produces both CPE and sphingomyelin, thus also functioning as a sphingomyelin synthase.[4] Both mammalian CPE synthases, SMS2 and SMSr, use phosphatidylethanolamine (PE) as head group donor and catalyzes the reaction

a ceramide + a phosphatidylethanolamine a ceramide-phosphoethanolamine + 1,2-diacylglycerol

Invertebrate Ceramide Phosphoethanolamine Synthases[edit]

SMSr protein is found in all organisms throughout the animal kingdom as a CPE synthase, yet it produces trace amounts of CPE.[5][6] Drosophila and a group of invertebrates lack SMS2 homologues.[5][6] This group of invertebrates synthesizes CPE using a particular enzyme called CPES.[6] CPES uses CDP-ethanolamine rather than phosphatidylethanolamine as head group donor, thus catalyzes the reaction [6]

a ceramide + a CDP-ethanolamine a ceramide-phosphoethanolamine + CMP

CPES uses a different reaction mechanism than the one sphingomyelin synthase uses, but very similar to that of enzymes involved in synthesis of phosphatidyl ethanolamine (EC via the Kennedy pathway.[7]


  1. ^ Malgat, M., Maurice, A., and Baraud, J. (1986) Sphingomyelin and ceramide-phosphoethanolamine synthesis by microsomes and plasma membranes from rat liver and brain. J. Lipid Res. 27, 251–260
  2. ^ Malgat, M., Maurice, A., and Baraud, J. (1987) Sidedness of ceramidephosphoethanolamine synthesis on rat liver and brain microsomal membranes. J. Lipid Res. 28, 138–143
  3. ^ Maurice, A., Malgat, M., and Baraud, J. (1989) Sidedness of ceramidephosphoethanolamine synthesis on rat liver plasma membrane. Biochimie 71, 373–378
  4. ^ a b c Ternes, P., Brouwers, J. F., van den Dikkenberg, J., and Holthuis, J. C. (2009) Sphingomyelin synthase SMS2 displays dual activity as ceramide phosphoethanolamine synthase. J. Lipid Res. 50, 2270–2277
  5. ^ a b c d Vacaru, A. M., Tafesse, F. G., Ternes, P., Kondylis, V., Hermansson, M., Browers, J. F. H. M., Somerharju, P., Rabouille, C., and Holthuis, J. C. (2009) Sphingomyelin synthase-related protein SMSr controls ceramide homeostasis in the ER. J. Cell Biol. 185, 1013–1027
  6. ^ a b c d Vacaru AM, van den Dikkenberg J, Ternes P, Holthuis JC. Ceramide phosphoethanolamine biosynthesis in Drosophila is mediated by a unique ethanolamine phosphotransferase in the Golgi lumen. J Biol Chem. 2013 Apr 19;288(16):11520-30. doi:10.1074/jbc.M113.460972. Epub 2013 Feb 28. PMID 23449981; PMC 3630839
  7. ^ KENNEDY EP, WEISS SB. The function of cytidine coenzymes in the biosynthesis of phospholipides. J Biol Chem. 1956 Sep;222(1):193-214. PMID 13366993.