Structural gangliosides

If there is no structural ganglioside abnormality in TSD, an enzymatic lesion along the degradative pathway must be considered. The alternate possibility, namely overproduction of sphingolipids, appears to be unlikely (see chapter of Burton, page 159). 

FIGURE 8.14 The structures of several important gangliosides. Also shown is a spacefilling model of ganglioside G i-... 

The glycosphingolipids (GSLs) are sugar-containing lipids built on a backbone of ceramide they include galactosyl- and glucosylceramide (cerebrosides) and the gangliosides. Their structures are described in Chapter 14. They are mainly located in the plasma membranes of cells. 

W. E. Minde, C. Roach, W. G. J. Hoi, and C. L. Verlinde, Structure-based exploration of the ganglioside GM1 binding sites of Escherichia coli heat-labile... 

Two of the most widely spread and well-studied enterotoxigenic forms of bacterial diarrhea are ETEC and Vibrio cholerae. The toxins they produce, labile toxin (LT) and cholera toxin (CT) respectively, are very similar in primary sequence, structure, and mechanism of action [72]. They are homologous multi-subunit proteins in which the non-toxic B subunit mediates GMj ganglioside binding, and thus are candidates for vaccines that can neutralize toxin activity. 

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. 

Yu, R. K. and Ando, S. Structures of some new complex gangliosides. In L. Svennerholm, P. Mandel, H. Dreyfus and P.-F. Urban (eds), Structure and Function of Gangliosides. New York Plenum Press, 1980, pp. 33M5. 

Addition of 5% ganglioside Gmi into the L-Glu-Bis-3 resulted in the appearance of vesicles along with twisted ribbons, while addition of nonchiral 10,12-docosadiynedioic acid caused the formation of platelets.97 These results affirm the importance of packing geometry, along with head group chirality, for the formation of helical structures. 

Among the gangliosides, GM4 [ct-NeuAc-(2 — 3)-/ -Gal-(l — 0)-Cer] has a relatively simple chemical structure. It has been detected in human and chicken brain and also (119) as a major ganglioside of mouse erythrocytes, chicken-embryonic liver, and egg yolk. With the help of the azidosphingo-sine glycosylation it has been synthesized very efficiently from the neuraminic acid-containing galactosyl donor 11a-/ (Table XI) (120-122). Similarly the thio isomer was obtained from lib-/ and (120,123) the positional isomer from llc-a. 

Figure 12.15 Gangliosides. The prefix mono-, di, tri- or tetra- denotes the number of sialic acid W-acetyl neuraminic acid, NANA) residues present in the molecule. The many different gangliosides have complex structures and for convenience shorthand notations are used. The two commonest were introduced by Svennerholm, who named the parent compound GM1, and Wiegnandt, who named it Ggnti. The latter system gives enough information for the structures to be worked out from the shorthand form once the symbols have been learnt. GalNAc represents N-acetyl galactosamine in the above structure.

A. A. Wolf, M. G. Jobling, S. Wimer-Mackin, M. Ferguson-Maltzman, J. L. Madara, R. K. Holmes, and W. I. Lencer. Ganglioside structure dictates signal transduction by cholera toxin and association with caveolae-like membrane domains in polarized epithelia. J Cell Biol. 141 917-927 (1998). 

The illustration shows a model of a small section of a membrane. The phospholipids are the most important group of membrane lipids. They include phosphatidylcholine (lecithin), phosphatidylethanolamine, phos-phatidylserine, phosphatidylinositol, and sphingomyelin (for their structures, see p. 50). in addition, membranes in animal cells also contain cholesterol (with the exception of inner mitochondrial membranes). Clycoli-pids (a ganglioside is shown here) are mainly found on the outside of the plasma membrane. Together with the glycoproteins, they form the exterior coating of the cell (the gly-cocalyx). 

The results of this study indicated that chloroplast-synthesized CTB-2L21 protein displays a strong affinity for GMl gangliosides in a similar manner to that found for purified bacterial CTB. This indicates that the fusion protein retained the correct pentameric structure characteristic of CTB and... 

A well-known receptor of CT is ganglioside Gmi its chemical structure is Gal-p-(l-... 

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