Abstract
Gangliosides are an important class of sialylated glycosphingolipids linked to ceramide that are a component of the mammalian cell surface, especially those of the central nervous system, where they function in intercellular recognition and communication. We describe an in silico method for determining the metabolic pathways leading to the most common gangliosides, based on the known enzymes of their biosynthesis. A network of 41 glycolipids is produced by the actions of the 10 enzymes included in the model. The different ganglioside nomenclature systems in common use are compared and a systematic variant of the widely used Svennerholm nomenclature is described. Knockouts of specific enzyme activities are used to simulate congenital defects in ganglioside biosynthesis, and altered ganglioside status in cancer, and the effects on network structure are predicted. The simulator is available at the Glycologue website, https://glycologue.org/.
Highlights
Gangliosides are glycosphingolipids that contain a sialylated carbohydrate linked to ceramide
The biosynthesis of gangliosides occurs in the endoplasmic reticulum and Golgi, where specific glycosyltransferases act, in stepwise fashion, by adding monosaccharides from sugar nucleotide donors, first to ceramide, and to subsequent ceramide-linked glycoconjugate acceptors, before transport and Beilstein J
We describe an extension of this method to gangliosides, and to the enzyme reactions associated with their biosynthesis
Summary
Gangliosides are glycosphingolipids that contain a sialylated carbohydrate linked to ceramide. In IUPAC form (see Table 1), we can write the carbohydrate portion of the ganglioside GM1a (Figure 1) as any of the following:
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