Structure of Glycosphingolipids

STRUCTURE OF GLYCOSPHINGOLIPIDS

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 (Figure 17.14 ). 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 (uncharged) 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 Figure 17.14 ) or glucose (forming ceramide-glucose or glucocerebroside, which serves primarily as 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 fatty acid attached to the sphingosine.] As their name implies, cerebrosides are found predominantly in the brain and peripheral nervous tissue, 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 Figure 17.15) in gangliosides, or by sulfate groups in sulfatides.

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. 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 Figure 17.15 for the structure of GM2.) Gangliosides are of medical interest because several lipid storage disorders involve the accumulation of NANA-containing glycosphingolipids in cells (see Figure 17.20).

Figure 17.15 Structure of the ganglioside G_M2. ( is a hydrophobic hydrocarbon chain.)

2. Sulfatides: These sulfoglycosphingolipids are sulfated galactocerebrosides that are negatively charged at physiologic pH. Sulfatides are found predominantly in the brain and kidneys.

Figure 17.20 Degradation of sphingolipids showing the lysosomal enzymes affected in related genetic diseases, the sphingolipidoses. All of the diseases are autosomal recessive except Fabry disease, which is X linked, and all can be fatal in early life. Cer = ceramide; Gal = galactose; Glc = glucose; GalNAc = N-acetylgalactosamine; NANA = N-acetylneuraminic acid; CNS = central nervous system. SO₄²- = sulfate.