Sphingosine N-

Igarashi, Y., and Hakomori, S., Enzymatic synthesis of N,N-dimethyl-sphingosine demonstration of the sphingosine N-methyltransferase in mouse brain, Biochem. Biophys. Res. Commun., 164, 1411,... 

Toxicity of fumonisins is caused by inhibition of the enzyme sphingosine N-acetyltransferase (ceramide synthase) due to the structural similarity of fumonisins with sphingosine (see Section 3.5.1.1.3). The toxic effects are closely related to the presence of the amino group in the molecule of fumonisin the reaction products with reducing sugars are virtually non-toxic as the amino group is blocked. Fumonisin B2 is more cytotoxic than fumonisin Bp... 

From experiments with CoA-activated fatty acids, Braun et al. (1970) concluded that the system responsible for the biosynthesis of ceramide is the one first suggested by Sribney (1966). Fatty acid is tied to a long-chain base by an acyltransferase, using fatty acyl-CoA as substrate. The authors also suggested that the specificity of the acyl-CoA sphingosine N-acyl transferase controls the distribution of the constituent fatty acids in ceramides. 

Other Names Hexanamide, (V-[2-hydroxy-l-(hydroxymethyl)-3-heptadecenyl]-6-[(7-nitro-2,l,3-benzoxadiazol-4-yl)amino]- Hexanamide, iV-[2-hydroxy-1 -(hydroxymethyl)-3-heptadecenyl]-6-[(7-nitro-4-benzofurazanyl)amino]- 2,1,3-Benzoxadiazole, hexanamide deriv. 6-((N-(7-Nitrobenz-2-Oxa-l,3-Diazol-4-yl)amino)hexanoyl)Sphingosine N-(6-[(7-nitrobenzo-2-oxa-1,3-diazo 1 -4-yl)amino] caproy 1 )-sphingosine ... 

Lipid phosphate phosphohydrolases (LPPs), formerly called type 2 phosphatidate phosphohydrolases (PAP-2), catalyse the dephosphorylation of bioactive phospholipids (phosphatidic acid, ceramide-1-phosphate) and lysophospholipids (lysophosphatidic acid, sphingosine-1-phosphate). The substrate selectivity of individual LPPs is broad in contrast to the related sphingosine-1-phosphate phosphatase. LPPs are characterized by a lack of requirement for Mg2+ and insensitivity to N-ethylmaleimide. Three subtypes (LPP-1, LPP-2, LPP-3) have been identified in mammals. These enzymes have six putative transmembrane domains and three highly conserved domains that are characteristic of a phosphatase superfamily. Whether LPPs cleave extracellular mediators or rather have an influence on intracellular lipid phosphate concentrations is still a matter of debate. 

Most GPCRs interact with and activate more than one G-protein subfamily, e.g., with Gs plus Gq/n (histamine H2, parathyroid hormone and calcitonin recqrtors), Gs plus G (luteinising hormone receptor, 32-adrenoceptor) or Gq/11 plus G12/13 (thromboxane A2, angiotensin ATb endothelin ETA receptors). Some receptors show even broader G-protein coupling, e.g., to Gi, Gq/n plus Gi n ( protease-activated receptors, lysophosphatidate and sphingosine-1-phosphate receptors) or even to all four G-protein subfamilies (thyrotropin receptor). This multiple coupling results in multiple signaling via different pathways and in a concerted reaction of the cell to the stimulus. 

The aziridine-2-carboxaldehyde 56 can also serve as synthon for the synthesis of sphingosines, which are important biomembrane constituents [64]. One possible route involves the addition of an alanate to the aldehyde. In a later stage of this synthetic plan the aziridine can be opened, either via the intermediacy of an oxazoline or directly with dilute acid. Unfortunately, the reaction of aldehyde 56 with a vinylalanate has a poor diastereoselectivity of 3 2. Therefore, an alternative approach was considered, namely one involving the addition of a vinylzinc reagent to the aldehyde thereby employing our N-tritylaziridinediphenyl-methanol 51 as the chiral catalyst. Gratifyingly, only one diastereomer was obtained. Reductive removal of the trityl function, acetylation of the hydroxy... 

C42H83NO9-0.5 C2H60 D-Dihydro-N-(2-D-hydroxyoctadecanoyl)-/ -D-galactosyl-sphingosine, ethanol solvate HCEREB 43 355... 

The amino group of sphingosine is acylated with long-chain fatty acids and the N-acylated product is termed a ceramide (Fig. 3-3). C-l of ceramide is linked to different... 

To prepare the desired D-mY/no-isomer D-30b, benzyl urethane 32 is prepared via the p-nitrophenylcarbonate 31 in a one pot reaction. Treating this N-nucleophile 32 with 5 equivalents of NaN(SiMe3)2 leads to the desired oxa-zolidine 33. Li/NH3 cleavage affords D-mY/no-sphingosine, which may also be characterized as its triacetate d-30 (Scheme 4-14). 

Auge, N., Nikolova-Karakashian, M., Carpentier, S., Parthasarathy, S., Negre-Salvayre, A., Salvayre, R., Merrill, A.H. Jr, Levade, T, 1999, Role of sphingosine 1-phosphate in the mitogenesis induced by oxidized LDL in smooth muscle cells via activation of sphingomyelinase, ceramidase, and sphingosine kinase, J. Biol. Chem. 274 21533-21538. 

Durieux, M.E., Carlisle, S.J., Salafranca, M.N. and Lynch, K.R., 1993, Responses to sphingosine-1 -phosphate in X. laevis oocytes Similarities with lysophosphatidic add signaling. Am. J. Physiol. 264 C1360-C1364. 

Ishizuka, T., Murata, N., Kanda, T., Kobayashi, I., Ohta, H., Ui, M. and Okajima, F., 1999, Comparison of intrinsic activities of the putative sphingosine 1-phosphate receptor sub-types to regulate several signaling pathways in their cDNA-transfected Chinese hamster ovary cells. J. Biol. Chem. 274 23940-23947. 

Moore, A.N., Kampfl, A.W., Zhao, X., Hayes, R.L. and Dash, P.K., 1999, Sphingosine 1-phosphate induces apoptosis of cultured hippocampal neuronsthat requires protein phosphatases and activator protein-1 complexes, 94 405-415. 

Pyne, S. and Pyne, N.J., 2000, Sphingosine 1-phosphate signaling in mammalian cells, Biochem. J. 349 385 2. 

Rakhit, S., Conway, A-M., Tate, R., Bower, T, Pyne, N.J. and Pyne, S., 1999, Sphingosine 1-phosphate stimulation of the p42/p44 mitogen-activated protein kinase pathway in airway smooth muscle role of endothelial differentiation gene-1, c-Src tyrosine kinase and phosphoinositide 3-kinase. Biochem. J. 338 643-649. 

Sakakura, C, Sweeney, E.A., Shirahama, T., Ruan, F., Solca, F., Kohno, M., Hakomori, S-1., Fischer, E.H. Igarashi, Y., 1997, Inhibition ofMAP kinase by sphingosine and its methylated derivative, N,N-dimethylsphingosine A correlation with induction of apoptosis in solid tumor cells,/nt/. 7. Oncol. 11 31-39. 

Yang, L., Yatomi, Y., Hisano, N., Qi, R., Asazuma, N., Satoh, K.., Igarashi, Y., Ozaki, Y. and Kume, S., 1996, Activation of protein-tyrosine kinase Syk in human platelets stimulated with lysophosphatidic acid or sphingosine 1 -phosphate. Biochem. Biophys. 

Yatomi, Y., Ruan, F Megidish, T., Toyokumi, T., Hakomori, S. and Igarashi, Y., 1996, N,N-dimethylsphingosine inhibition of sphingosine kinase and sphingosine 1-phosphate activity in human platelets, Biochem. J. 35 626-633. 

Zhang, H., Desai, N.N., OUvera, A., Seki, T., Brooker, G. and Spiegel, S., 1991, Sphingosine-1-phosphate, a novel hpid, involved in cellular prohferation. J. Cell Biol. 114 155-167. 

Shayman, J. A., Deshmukh, G. D., Mahdiyoun, S., Thomas, T. P., Wu, D., Barcelon, E. S., and Radin, N. S., 1991, Modulation of renal epithehal cell growth by glucosylceiamide. Association with protein kinase C, sphingosine, and diacylglycerol. J. Biol, Chem. 266 22968-22974. 

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