THE CHEMICAL CONSTITUTION OF GANGLIOSIDES OF THE VERTEBRATE NERVOUS-SYSTEM

Glycosphingolipids are uniquely distinguished amongst the glycoconjugates by the apparently systematic structuring of their ceramide-linked carbohydrate moieties. These often highly complex oligosaccharides provide a structural repertoire that may vary considerably according to cell types and animal species. However, as a possible reflection of their specific functional role in the central nervous system, the brain glycosphingolipids of all vertebrates follow the same principles of carbohydrate structuring with only minor variations: the anabolically early addition of sialic acid to lactosylceramide (Gal beta 4Glc beta Cer-->NeuAc alpha 3Gal beta 4Glc beta Cer) in central nervous tissue results in the preferential formation of 'gangliosides', i.e., sialic acid-containing glycosphingolipids. Higher gangliosides result from extensions of sialo-lactosylceramide by addition of nucleotide-activated monosaccharides. In consequence, gangliosides of the vertebrate central nervous system consist of ceramide-linked sialo-oligosaccharides of varying chain length with a ganglio-series core carbohydrate, i.e., GalNAc beta 4Gal beta 3GalNAc beta 4Gal beta 4Glc beta<0. Substitution by mono-, bis-, or tris-sialo-groups may variably be at the galactoside- and N-acetylgalactosaminide residues in 3- and B-positions of the ganglio-series oligosaccharides, respectively. Ganglioside, which is derived by sialylation of galactosylceramide, NeuAc alpha 3Gal beta Cer, is a characteristic constituent of glial cells. In nerve tissue, gangliosides of the lacto-(Gal beta(3GlcNAc beta 3Gal beta)(n)4Glc beta<) and the neolacto-series (Gal beta(4GlcNAc beta 3Gal beta)(n)4Glc<) are more characteristic of vertebrate peripheral nerves and neuroectoderm-derived tumours. Recent studies using monoclonal antibodies have revealed that various single ganglioside components are specifically distributed in nervous tissues. This finding adds a new dimension to the earlier notion that gangliosides are involved in membrane related phenomena including cell to cell interactions, as well as, the modulation of signalling mechanisms.