Salvage pathways in glycosphingolipid metabolism

• Published in: Biochimie Vol. 85; no. 3; pp. 423 - 437
• Main Authors: Tettamanti, G, Bassi, R, Viani, P, Riboni, L
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.03.2003
• Subjects: Animals; Carbohydrate Sequence; Cell Membrane - metabolism; Ganglioside metabolism; Gangliosides - chemistry; Gangliosides - metabolism; Glycosphingolipid metabolism; Glycosphingolipid salvage pathways; Glycosphingolipids - chemistry; Glycosphingolipids - metabolism; Glycosylation; Humans; In Vitro Techniques; Membrane Lipids - chemistry; Membrane Lipids - metabolism; Molecular Sequence Data; Molecular Structure; Oligosaccharides - chemistry; Oligosaccharides - metabolism; Sphingoid bioregulators; Subcellular Fractions - metabolism; Cer; Glycosphingolipid salvage pathways; Ganglioside metabolism; Gal; Sphingoid bioregulators; Glycosphingolipid metabolism; The code system for gangliosides and allied glycosphingolipids suggested by Svennerholm [L. Svennerholm, Ganglioside designation, in: L. Svennerholm, P. Mandel, H. Dreyfus, P.F. Urban (Eds.), Structure and Function of Ganglioside, vol. 125, Adv. Exp. Med. Biol., Plenum Press, New York, 1980, p. 11]; NeuAc; Sph; Glc; GalNac; Lac
• ISSN: 0300-9084; 1638-6183
• DOI: 10.1016/S0300-9084(03)00047-6

In this review, the focus is on the role of salvage pathways in glycosphingolipid, particularly, ganglioside metabolism. Ganglioside de novo biosynthesis, that begins with the formation of ceramide and continues with the sequential glycosylation steps producing the oligosaccharide moieties, is briefly outlined in its enzymological and cell-topological aspects. Neo-synthesized gangliosides are delivered to the plasma membrane, where their oligosaccharide chains protrude toward the cell exterior. The metabolic fate of gangliosides after internalization via endocytosis is then described, illustrating: (a) the direct recycling of gangliosides to the plasma membrane through vesicles gemmated from sorting endosomes; (b) the sorting through endosomal vesicles to the Golgi apparatus where additional glycosylations may take place; and (c) the channelling to the endosomal/lysosomal system, where complete degradation occurs with formation of the individual sugar (glucose, galactose, hexosamine, sialic acid) and lipid (ceramide, sphingosine, fatty acid) components of gangliosides. The in vivo and in vitro evidence concerning the metabolic recycling of these components is examined in detail. The notion arises that these salvage pathways, leading to the formation of gangliosides and other glycosphingolipids, sphingomyelin, glycoproteins and glycosaminoglycans, represent an important saving of energy in the cell economy and constitute a relevant event in overall ganglioside (or glycosphingolipid, in general) turnover, covering from 50% to 90% of it, depending on the cell line and stage of cell life. Sialic acid is the moiety most actively recycled for metabolic purposes, followed by sphingosine, hexosamine, galactose and fatty acid. Finally, the importance of salvage processes in controlling the active concentrations of ceramide and sphingosine, known to carry peculiar bioregulatory/signalling properties, is discussed.