Tay-Sachs ganglioside

The ganglioside GM1 contains another galactose residue joined in (3-linkage to the 3-position of iV-acetylgalactosamine of Tay Sachs ganglioside and asialo GM1 thus has the structure ... 

To determine the structure in more detail, Svennerholm treated the gangliosides with neuraminidase to remove the A/ -acetylneuraminic acid. This resulted in an asialoganglioside that was much easier to analyze. He hydrolyzed it with acid, collected the ceramide-containing products, and determined the molar ratio of the sugars in each product. He did this for both the normal and the Tay-Sachs gangliosides. His results are shown below. 

Svennerholm, L. (1962) The chemical structure of normal human brain and Tay-Sachs gangliosides. Biochem. Biophys. Res. Comm. 9, 436-441. 

Svennerholm152 found that the molecular ratios of the lipid and sugar residues of the Tay-Sachs ganglioside are ceramide hexose 2-acetamido-2-deoxy-D-galactose N-acetylneuraminic acid = 1 2 1 1. 

From the Tay-Sachs ganglioside (81), N-acetylneuraminic acid can be cleaved enzymically, to give the ceramide trisaccharide. By degradation with ozone, or by mild hydrolysis, a trisaccharide is obtained, namely,... 

Starting from ceramide D-glucoside, enzymic synthesis has been studied for producing gangliosides222,223 and for the conversion of Tay-Sachs ganglioside into monosialoganglioside by the uridine 5 -pyrophosphate of brain.224... 

GMi gauglkwide GM> Tay-Sachs) ganglioside Triliexosylcera mide Glucosylceiamide Sphingomyelin Ceramide... 

The Tay-Sachs ganglioside (Gm2) has been prepared which is specifically labelled in either the AT-acetylneuraminosyl or N-acetylgalactosaminyl portions (Tallman et aL, 1975). For the first type of labelling, Ghi is an intermediate and, for the second, Gh3 is isolated from erythrocytes first and then converted to Gm2-... 

Pioneer studies on the structure of this Tay-Sachs ganglioside, with the use of partial acid hydrolysis, periodate oxidation and exhaustive methylation, have been performed simultaneously by... 

Histologic and histochemical properties of material from brain biopsy or rectum biopsy render further evidence for the diagnosis, and secure to some degree the differentiation of TSD from other types of amaurotic family idiocy. Lipid analyses from brain tissue with the demonstration of the increase in Tay-Sachs ganglioside finally provide conclusive evidence for the diagnosis. 

The following discussion summarizes available information on structure and metabolism of the Tay-Sachs gangliosides. Pathogenetic discussions center once more on two questions ... 

Extensive studies on the chemical structure of the Tay-Sachs ganglioside have not shown a significant abnormality. As mentioned earlier, a compound with identical structure has been found among brain gangliosides of normal subjects. However, the sensitivity of these complex molecules toward treatment with alkali or acid, the possibility of spontaneous hydrolysis during handling and the complicated methods of structural identification render definite clarification of this point difficult. 

One possibility is impaired liberation of N-acetyl-galactosamine as proposed by Svennerholm (1957b). A defective removal of a carbohydrate moiety from a mono-sialoganglioside is also assumed by Rouser et al. (1965), since other gangliosides can be degraded to the Tay-Sachs ganglioside by neuraminidase. 

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