Ganglioside activity

Comparing the activity of the Mg2+-ATPase in the presence of water suspensions of gangliosides and phosphatidylserine it was found that only the gangliosides activated. However, when sodium-deoxycholate (0.06 mM) was added to the incubation medium phospha-tidylserine also activated the enzyme. 

Ben-Yoseph, Y., Mitchell, D. A., Yager, R. M., and Pretzlaff, R. K., 1991, Stimulation of GM3 ganglioside activity by an activator protein in patient with mucolipidosis IV and controls. Enzyme 45 23-29. 

In the second example, the synthesis of an I-active ganglioside analogue98 is covered. The sialyl I antigen is shown in Scheme 14. 

Glycosphingolipids are constituents of the outer leaflet of plasma membranes and are important in cell adhesion and cell recognition. Some are antigens, eg, ABO blood group substances. Certain gangliosides function as receptors for bacterial toxins (eg, for cholera toxin, which subsequently activates adenylyl cyclase). 

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. 

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]. 

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... 

In contrast to this work on whole brain, Kemp and Stoolmiller138 used cultured mouse-neuroblastoma cells for their study of incorporation of [ lH]2-acetamido-2-deox> -D-mannose into the sialic acid moiety of gangliosides. They were able to demonstrate clearly the precursor-product relationship among CMS, GM2, and GM1. They found that cultured NB41A cells incorporated [3H]2-acetamido-2-deoxy-D-man-nose into the sialic acid moiety of GM3 in less than 10 minutes. Labeled GM2 was not detected in cells incubated for less than 30 minutes, and measurable activity did not appear in G I1 until alter 60 to 90 minutes. These results further supported the concept that the pathway of synthesis of ganglio-tvpe gangliosides proceeds by way of GM3 —> GM2 — GM1. 

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