Ceramide phosphoethanolamine synthase
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 2.7.8.1) via the Kennedy pathway.[7]
References
[edit]- ^ Malgat, M.; Maurice, A.; Baraud, J. (1986). "Sphingomyelin and ceramide-phosphoethanolamine synthesis by microsomes and plasma membranes from rat liver and brain". J. Lipid Res. 27 (3): 251–260. doi:10.1016/S0022-2275(20)38834-9. PMID 3734625.
- ^ Malgat, M.; Maurice, A.; Baraud, J. (1987). "Sidedness of ceramidephosphoethanolamine synthesis on rat liver and brain microsomal membranes". J. Lipid Res. 28 (2): 138–143. doi:10.1016/S0022-2275(20)38715-0. PMID 3033117.
- ^ Maurice, A.; Malgat, M.; Baraud, J. (1989). "Sidedness of ceramidephosphoethanolamine synthesis on rat liver plasma membrane". Biochimie. 71 (3): 373–378. doi:10.1016/0300-9084(89)90009-6. PMID 2525931.
- ^ a b c Ternes, P.; Brouwers, J. F.; van den Dikkenberg, J.; Holthuis, J. C. (2009). "Sphingomyelin synthase SMS2 displays dual activity as ceramide phosphoethanolamine synthase". J. Lipid Res. 50 (11): 2270–2277. doi:10.1194/jlr.M900230-JLR200. PMC 2759833. PMID 19454763.
- ^ 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.; Holthuis, J. C. (2009). "Sphingomyelin synthase-related protein SMSr controls ceramide homeostasis in the ER". J. Cell Biol. 185 (6): 1013–1027. doi:10.1083/jcb.200903152. PMC 2711605. PMID 19506037.
- ^ a b c d Vacaru, AM; van den Dikkenberg, J; Ternes, P; Holthuis, JC (2013). "Ceramide phosphoethanolamine biosynthesis in Drosophila is mediated by a unique ethanolamine phosphotransferase in the Golgi lumen". J Biol Chem. 288 (16): 11520–30. doi:10.1074/jbc.M113.460972. PMC 3630839. PMID 23449981.
- ^ Kennedy, EP; Weiss, SB (Sep 1956). "The function of cytidine coenzymes in the biosynthesis of phospholipides". J Biol Chem. 222 (1): 193–214. doi:10.1016/S0021-9258(19)50785-2. PMID 13366993.
