Ceramides and gangliosides

In all glycosyl ceramides and gangliosides there is an O-glycosidic linkage between the primary hydroxyl of sphingosineand C-1 of the sugar... 

Because membranes components participate in nearly every cell activity their structures are also dynamic and far from the equilibrium states that are most readily understood in biophysical terms. Newly synthesized bilayer lipids are initially associated with endoplasmic reticulum (Ch.3) whereas phospholipids initially insert into the cytoplasmic leaflet while cholesterol and sphingolipids insert into the luminal endoplasmic reticulum (ER) leaflet. Glycosylation of ceramides occurs as they transit the Golgi compartments, forming cerebrosides and gangliosides in the luminal leaflet. Thus, unlike model systems, the leaflets of ER membranes are asymmetric by virtue of their mode of biosynthesis. 

The exact role of ceramide in apoptosis seems not to be clear because of problems detecting ceramide levels (Kolesnick and Hannun, 1999 Hofmann and Dixit, 1999 Watts et al, 1999). Ganglioside GD3 is an important mediator of Fas-induced apoptosis in hematopoietic cells. Ceramide triggers the synthesis of ganglioside GD3 (DeMaria et al., 1997). So it is difficult to explain vdiether the inducer of apoptosis is ceramide or ganglioside. 

Both protein- and lipid-bound carbohydrates are present in milk lipid globule membrane (Table 10.2). Lipid-bound carbohydrates, present predominantly in glucosyl and lactosyl ceramides and in gangliosides,... 

This problem was approached by incorporating radioactive percur-sors into the glycolipids of both brain and lymphoma cells of the Thy-1.2 and 1.1 types. We have used C-palmitate as a per-cursor of ceramide, and - C-N-acetylmannosamine as a percursor of sialic acid (7). Glycolipids were isolated and the radioactive gangliosides were resolved by two-dimensional thin layer chromatography in two different solvent systems followed by autoradiography. 

ApcUm/+ mice were fed a control diet or that diet supplemented with either 0.1% ceramide, a sphingolipid mixture of sphingomyelin, glucosylcer-amide, lactosylceramide and ganglioside GD3 with a composition similar to that found in dairy products, or this mixture plus ceramide (60 40). All three diets significantly reduced the number of spontaneously developed tumors in all regions of the intestines (Schmelz et al., 2001). 

Figure 26.3. Synthesis of Sphingolipids. Sphingosine is converted into ceramide, which is an intermediate in the formation of sphingomyelin and gangliosides.

C. Palmitoyl CoA and serine react to form a precursor that is converted to sphingosine. Sphingosine does not contain a glycerol moiety. Formation of an amide with a fatty acyl CoA converts sphingosine to ceramide. Ceramide may be converted to sphingomyelin, cerebrosides, and gangliosides. 

Sphingosine is a precursor of ceramide from which sphingomyelin, cerebrosides, and gangliosides are produced (see Figure 6-15). 

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