Gangliosides are sialic acid-containing glycosphingolipids. They occur especially on the cellular surfaces of neuronal cells, where they form a complex pattern, but are also found in many other cell types. The paper provides a general overview on their structures, occurrence, and metabolism. Key functional, biochemical, and pathobiochemical aspects are summarized. 1. Introduction Together with glycoproteins and glycosaminoglycans, glycosphingolipids (GSLs) contribute to the glycocalyx that covers eukaryotic cell surfaces. Gangliosides are sialic acid-containing glycosphingolipids and provide a significant part of cell surface glycans on neuronal cells. GSLs are lipids that contain a sphingoid base and one or more sugar residues [1]. Sialic acids (Figure 1) are nine-carbon sugars biosynthetically formed from -acetylmannosamine and phosphoenolpyruvate [2, 3]. With a mean value of around 2.6, they are more acidic than the majority of carboxylic acids and negatively charged at most physiological pH values. The name “ganglioside” was coined by the German biochemist Klenk (1896–1971) and assigned to a group of acidic GSLs that he isolated from ganglion cells [4, 5] and from the brains of patients who suffered from the so-called amaurotic idiocy [6, 7]. Sialic acid was first isolated from submaxillary mucin in 1936 [8]. Its structure was elucidated in the nineteen fifties by different groups and it was found to be identical to that of the N-acetylneuraminic acid isolated by Klenk and Faillard. The first structure of a ganglioside was elucidated in 1963 by Kuhn and Wiegandt [9]. In 1962, Svennerholm suggested a nomenclature of brain gangliosides [10, 11]. The biochemical defects underlying the diseases formerly known as amaurotic idiocy, GM1-gangliosidosis [12], Tay-Sachs- [13], and Sandhoff disease [14] were identified by Sandhoff and others in the 1960s. Figure 1: Sialic acids. 2. Structure and Nomenclature In their structures, gangliosides combine a glycan and a lipid portion and contribute to both, the cellular lipidome and the glycome/sialome [15]. A great variety of carbohydrate sequences are found within the GSLs [16], including the gangliosides [17]. Although carbohydrate residues of different structure, linkage, and anomeric configuration occur in GSLs, only a limited number of the so-called series with characteristic carbohydrate sequences are found within evolutionary related organisms (Table 1). Within the gangliosides, sialic acids can be attached only to a few of the GSL series, in adult mammals especially to the ganglio series. Table 1: GSL
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