Sphingolipids gangliosides

Pan and Charych, after their pioneering work for virus detection by PDA platform, extended its application for detection of cholera toxins. Initially, they employed sphingolipid gangliosides (Figure 10.7) along with 5,7-dicosadiynoic acid for him... 

Figure 10.7. The structure of the sphingolipid ganglioside GMl used for detecting cholera toxin is shown.

Fig. 14.—Schematic Representation of the Fragmentation Observed in the Positive F.a.b.-Mass Spectrum of a Permethylated Ganglioside Isolated from Granulocytes. [Other glyco-sphingolipids fragment in a similar way. Major cleavages are shown with solid lines, and minor cleavages with dotted lines. The masses of ions resulting from cleavages (a), (b), and (c) define the type of sphingosine and the type of fatty acid. In this example, (a) is 548, (b) is [M + H] minus 238, and (c) is [M + H] minus 533.]...

Sphingolipids (ceramids, sphingomyelin, cerebrosides, sulfatides, gangliosides) and lipids with secondary amines produce blue spots on a white backgound (CAUTION benzidine is a carcinogen)... 

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. 

FIGURE 3-3 Structure of some simple sphingolipids. X may be a complex polysaccharide either containing sialic acid (gangliosides) or not (globosides). See also Figures 3-4 and 3-9 for the nomenclature and structure of some of the complex brain sphingolipids. 

In general the sphingolipids are located on the exterior face of a membrane while the phospholipids make up the inner face. This is understandable when we recall that sphingolipids include the gangliosides and cerebrosides whose polar ends contain carbohydrates or complex carbohydrate derivatives. The large number of chiral centers in carbohydrate molecules offer a complex pattern on the surface of the membrane which can impart a large degree of specificity for a particular cell type. The composition and limited fluidity of the bilayer make the entire membrane asymmetric, that is, different on the inner and outer layers or leaflets. 

Hexoseamidase A is the enzyme which is deficient in Tay-Sachs disease. This inherited condition results in an accumulation of GM2 gangliosides (sphingolipids) in the brain. The consequences are mental retardation, paralysis, blindness and death by the age of 3-4 years. 

Gangliosides, the most complex sphingolipids, have oligosaccharides as their polar head groups and one or more residues of Ai-acetylneuraminic acid (Neu5Ac), a sialic acid (often simply called sialic acid ), at the... 

Conformational restriction of biologically flexible molecules is a successful strategy in drug development. Application of this concept to ceramide, the membrane anchor of sphingolipids, led to the unexpected inhibition of glycosyltransferases involved in the combinatorial biosynthesis of gangliosides. This discovery offers a new approach to cell surface engineering. 

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