Glycosphingolipid Structure

The glycosphingolipids differ from sphingomyelin in that they do not contain phosphate, and the polar head function is provided by a monosaccharide or oligosaccharide attached directly to the ceramide by an O-glycosidic bond (Fig. 1). The number and type of carbohydrate moieties present determine the type of glycosphingolipid.

Figure 17.14 Structure of a neutral glycosphingolipid, galactocerebroside. ( is a hydrophobic hydrocarbon chain.)
A. Neutral glycosphingolipids
The simplest neutral glycosphingolipids are the cerebrosides. These are ceramide monosaccharides that contain either a molecule of galactose (forming ceramide-galactose or galactocerebroside, the most common cerebroside found in myelin, as shown in Fig. 1) or glucose (forming ceramide-glucose or glucocerebroside, an intermediate in the synthesis and degradation of the more complex glycosphingolipids). [Note: Members of a group of galacto- or glucocerebrosides may also differ from each other in the type of FA attached to the sphingosine.] As their name implies, cerebrosides are found predominantly in the brain and peripheral nerves, with high concentrations in the myelin sheath. Ceramide oligosaccharides (or globosides) are produced by attaching additional monosaccharides to a glucocerebroside, for example, ceramide-glucose-galactose (also known as lactosylceramide). The additional monosaccharides can include substituted sugars such as N-acetylgalactosamine.
B. Acidic glycosphingolipids
Acidic glycosphingolipids are negatively charged at physiologic pH. The negative charge is provided by N-acetylneuraminic acid ([NANA], a sialic acid, as shown in Fig. 2) in gangliosides or by sulfate groups in sulfatides.

Figure 2: Structure of the ganglioside GM2. ( is a hydrophobic hydrocarbon chain.)
1. Gangliosides: These are the most complex glycosphingolipids and are found primarily in the ganglion cells of the CNS, particularly at the nerve endings. They are derivatives of ceramide oligosaccharides and contain one or more molecules of NANA (from CMP-NANA). The notation for these compounds is G (for ganglioside) plus a subscript M, D, T, or Q to indicate whether there is one (mono), two (di), three (tri), or four (quatro) molecules of NANA in the ganglioside, respectively. Additional numbers and letters in the subscript designate the monomeric sequence of the carbohydrate attached to the ceramide. (See Fig. 2 for the structure of GM2.) Gangliosides are of medical interest because several lipid storage disorders involve the accumulation of NANA-containing glycosphingolipids in cells .
2. Sulfatides: These sulfoglycosphingolipids are sulfated galactocerebrosides that are negatively charged at physiologic pH. Sulfatides are found predominantly in the brain and kidneys.