Synthases sphingomyelin

Figure 1. Pathways for the synthesis of phosphatidylcholine, phosphatidylethanolamine and sphingomyelin. Abbreviations CK, choline kinase CPT, cholinephosphotransferase CT, CTP phosphooholine cytidylyltransferase DAG, diacylglycerol PC, phosphatidylcholine PE, phosphatidylethanolamine PEMT, phosphatidylethanolamine-N-methyltransferase SM, sphingomyelin SMase, sphingomyelinase SMsyn, sphingomyelin synthase.

Luberto, C., and Hannun, Y. A., 1998, Sphingomyelin synthase, a potential regulator of intracellular levels of ceramide and diacylglycerol during SV40 transformation. Does sphingomyelin synthase account for the putative phosphatidylcholine-specific phospholipaseC /. Biol. Chem. 273 14550-14559. 

Ceramide formed in mammalian systems is metabolized to sphingomyelin, glycosphingolipids, and ceramide 1-phosphate by the actions of sphingomyelin synthase, glucosylceramide synthase, and ceramide kinase on ceramide, respectively. Ceramide synthesized in the endoplasmic reticulum is transported to the Golgi apparatus for synthesis of complex sphingolipids (93). Sphingomyelin is synthesized from ceramide by transfer of the... 

Figure 12 Structures of synthetic inhibitors of sphingomyelin synthase, ceramidases, p-glucosylceramide synthase, dihydroceramide desaturase, and SI P lyase.

Meng A, Luberto O, Meier P, Bai A, Yang X, Hannun YA, Zhou D. Sphingomyelin synthase as a potential target for D609-induced apoptosis in U937 human monocytic leukemia cells. Exp. Cell Res. 2004 292 385-392. 

Alphonse et al., 2002). Ceramide can also be increased by the inhibition of ceramide breakdown by ceramidase and the inhibition of sphingomyelin synthase. 

Overexpression of Sphingomyelin Synthase Induces Lipoprotein Patterns That Correlate With Increased Cardiovascular Risk... 

However, other experimental observations do not quite fit this model that centers on the physical interaction of sphingomyelin with cholesterol and current data suggest at least one other level of regulation. For example, 25-hydroxy-cholesterol and ceramide both increase sphingomyelin mass but decreases SREBP and SRE-mediated gene transcription (Ridgway, 1995 Sakai et al., 1996).Ceramide dose-dependently decreases SREBP and HMG-CoA synthase activity by a mechanism independent of a cholesterol-mediated decrease of SREBP (Ridgway and Merriam, 1995). 

Huitema K, van den Dikkenberg J, Brouwers JF, Holthuis JC. Identification of a family of animal sphingomyelin synthases. Embo / 23(2004) 33 4. 

Tafesse FG, Ternes P, Holthuis JC. The multigenic sphingomyelin synthase family. J Biol Chem 281(2006) 29421-29425. 

Van der Luit, A.H., Budde, M., Zerp, S., Caan, W., Klarenbeek, J.B., Verheij, M., and Van Blitterswijk, W.J. Resistance to alkyl-lysophospholipid-induced apoptosis due to down-regulated sphingomyelin synthase 1 expression with consequent sphingomyelin- and cholesterol-deficiency in lipid rafts. Biochem J, 401, 2007, 541-549. 

Elmendorf, H. G. and Haidar, K. (1994) Plasmodium falciparum exports the Golgi marker sphingomyelin synthase into a tubulovesicular network in the cytoplasm of mature erythrocytes. J. Cell Biol. 124 449-462. 

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