Sialidase gangliosides

Several ganglioside analogs containing an a-thioglycoside of sialic acid, derived for example from (29 c) (Scheme 8), have been found to be potent inhibitors of sialidase activities of different subtypes of influenza virus [64]. 

The aeylneuraminic acids can be released from their glycosidic linkages either by dilute (aqueous or methanolie) acids or sialidases. Special care must be taken in the isolation of the rather labile, O-acv-lated sialic acids, which arc partially non-susceptible to the action of sialidases. Furthennore, in gangliosides, non-O-acetylated sialic acid residues occur, and these are also more or less resistant towards these enzymes. 

Apart from the 4-O-acetylated sialic acids, another sialidase-resist-ant sialic acid exists in Nature, namely, the internal, Gal-bound, sialic acid residue of GM,. In contrast to this side-positioned sialic acid, the sialyl residues bound to the peripheral Gal of gangliosides, or to both the peripheral and the internal sialic acid residues forming oligo-sialvl chains in several members of the large ganglioside family,la can be readily removed by sialidases, as was tested with viral, bacterial, and mammalian enzymes.35 -35 1... 

The substrate-specificity studies described in this Subsection show striking similarities between the sialidases from various sources, but also characteristic differences with regard to the N- and O-substitu-tions of Neu, the sialic acid glvcosidic linkages, and the oligosaccharide, glycoprotein, or ganglioside nature of the substrates.55... 

Variable sialidase activities are known to occur physiologically during ontogenesis."0 In chick retina, the lowest enzyme activity was observed in the 8-day-old embryo, whereas the highest activity was measured at hatching. Gangliosides were shown to be the best substrates... 

Exposure of HeLa cells to butyrate had no effect on the activity of GM3-sialidase when GM3 specifically labeled in the sialic acid residue was used as substrate (Fig. 3a). We were unable to detect any "ecto"-sialidase activity in either control or butyrate-treated cells (14) although others have postulated that such an enzyme is important in regulating plasma membrane gangliosides (15,16). In contrast, the activity of the specific sialyl transferase involved in GM3 biosynthesis increased over 20-fold following butyrate treatment (Fig. 3b). The effect was specific as activities of the other glycosphingolipid transferases that could be measured in HeLa cells were not altered in butyrate-treated cells (4,8,17). 

Gangliosides. sialidase and sialvltransferase in the membranes surrounding nerve endings ( synaptosomal membranes )... 

Figure 8. Location of gangliosides, sialidase, and sialyltransferase at the nerveending membrane...

Figure 12. Time course of NeuAc release from liposome-associated ganglioside Gn,a by the action of Vibrio cholerae sialidase...

U) Incubation of enzyme-susceptible tissues with Vibrio ahoterae sialidase increased the number of binding sites proportional to the increase in GM1 ganglioside, as well as increased cellular sensitivity to the toxin (9.). 

Figure 5. Effect of hydrolysis of plastic-attached gangliosides with V. cholerae sialidase on their binding capacity for tetanus (%) and cholera toxins as determined by ganglioside-ELlSA method...

King, C.A. van Heyningen, W.E. Deactivation of cholera toxin by a sialidase-resistant monosialosyl-ganglioside. 

Y. Suzuki, K. Sato, M. Kiso, and A. Hasegawa, New ganglioside analogs that inhibit influenza virus sialidase, Glycoconj. J., 7 (1990) 349-354. 

There are other lysosomal disorders in addition to those shown in Figure 9.20 and Table 9.1. For instance, several types of fucosidoses exist, which affect such structures as glycoproteins and blood group substances. Sialidoses also exist. However, lysosomal fucosidase and sialidase (neuraminidase) deficiencies do not affect the degradation of gangliosides. 

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