Glucosyl-ceramide

GM, Galactosyl-A/-acetylgalactosaminyl-(neuraminosyl)-galactosyl- glucosyl-ceramide... 

GD3 (disialohematoside) Neuraminosyl-(2 -> 8)-neuraminosyl-(2 - 3)-galactosyl-glucosyl-ceramide... 

As shown in figure 19.12, ceramide is also the precursor of glucosyl-ceramide, the simplest member of the glycosphin-golipids. The biosynthesis of glycosphingolipids shows... 

Shapiro and co-workers have described [89] (in a paper submitted just before the death of this pioneer in the field of glycosphingolipid synthesis — for a review of his extensive work in this area see Ref. [1]) a synthesis of the thio-analogue (88) of glucosyl ceramide (and the saturated derivative) from 2,3,4,6-tetra-0-acetyl-l-mercapto- 3-D-glucopyranose (86) and the 1-deoxy-l-iodoceramide derivative (85) in the presence of l,8-diazabicyclo[5.4.0]undec-7-ene. The product (87) was deacylated with methano-lic barium methoxide to give (88). 

Wynn et al. have described a potential energy calculation which utilizes the non bonded interaction and a term for the electrostatic interaction with the inclusion of directed chargers , localized in certain atomic orbitals [192, 193]. With this potential, they obtained for the P-D-glucosyl-ceramide a conformation which is similar to the X-ray crystal structure of P-D-Gal-ceramide [194], The calculation of the a-D-NeuvVAc-(2-3)-P-o-Gal disaccharide shows a conformation with cp-ci = 120° (determined from the stereoplot presented in the publication) which is inconsistent with the data obtained by Sabesan et al. [191], who were able to show that their calculated conformation with (p = 165° is in agreement with NOE data. 

Fredrickson, D.S. (1979). Gaucher s disease (glucosyl ceramide lipidosis). In Cecil Textbook of Medicine. P.B.Beeson, W.McDermott, and J.B.Wyngaarden, eds. (London W.B.Saunders), pp. 2012 2014. 

Jennemann R, Sandhoff R, Langbein L, Kaden S, Rothermel U, Gallala H, Sandhoff K, Wiegandt H, Gome HJ. Integrity and barrier function of the epidermis critically depend on glucosyl-ceramide synthesis. J. Biol. Chem. 2007 282 3083-3094. Kinoshita T, Ohishi K, Takeda J. GPI-anchor synthesis in mammalian cells genes, their products and deficiency. J. Biochem. 1997 122 251-257. 

Figure 1 Structure of the glycosphingolipid, globotriaosyl ceramide. Gal 1 -4 Cain 1 -4 glucosyl ceramide. The three lowest energy conformations as calculated by molecular modeling (3) are shown.

MDRl is a member of a family of ATP-dependent drug efflux pumps (32). Several of these pumps, including MDRl, have been shown to mediate lipid translocation and phospholipid bilayers (33). This translocation activity has been implicated in part as the mechanism for dmg efflux by which the hydrophobic cytotoxic drug is translocated from the cytosolic to the external leaflet of the plasma membrane bilayer. MDRl first was shown to translocate glucosyl ceramide analogs from the cytosolic to the external leaflet of the plasma membrane (33). However, the major glucosyl ceramide translocation activity of MDRl later... 

Figure 5 Structure of chemical inhibitors of glucosyl inhibitors of glucosyl ceramide synthase PDMP and hydroxy P4.

Table 1 Mass spectroscopy of oxidized glucosyl ceramide that shows that the oxidation procedure allows the quantitation of a degree of unsaturation within the fatty acid moiety (taken from Reference 136)...

Figure 8 Comparison of NDB- and BODIPY-labeled lyso glucosyl ceramide and NBD-labeled amino acyl glucosyl ceramide (147).

Glucosyl ceramide (GLia) GlcjSl Cer Major neutral glycolipid in central nervous system... 

Gaucher s disease (glucosyl ceramide lipidosis three types see text)... 

K. K.A., Cammue, B.P.A. Defensins from insects and plants interact with fungal glucosyl-ceramides. /. Biol. Chem. 2004, 279, 3900-3905... 

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