Sugar-containing lipid molecules called glycolipids have the most extreme asymmetry in their membrane distribution: these molecules, whether in the plasma membrane or in intracellular membranes, are found exclusively in the monolayer facing away from the cytosol. In animal cells, they are made from sphingosine, just like sphingomyelin (see Figure 10–3). These intriguing molecules tend to self-associate, partly through hydrogen bonds between their sugars and partly through van der Waals forces between their long and straight hydrocarbon chains, which causes them to partition preferentially into lipid raft phases (see Figure 10–13). The asymmetric distribution of glycolipids in the bilayer results from the addition of sugar groups to the lipid molecules in the lumen of the Golgi apparatus. Thus, the compartment in which they are manufactured is topologically equivalent to the exterior of the cell (discussed in Chapter 12). As they are delivered to the plasma membrane, the sugar groups are exposed at the cell surface (see Figure 10–15), where they have important roles in interactions of the cell with its surroundings.
Glycolipids probably occur in all eukaryotic cell plasma membranes, where they generally constitute about 5% of the lipid molecules in the outer monolayer. They are also found in some intracellular membranes. The most complex of the glycolipids, the gangliosides, contain oligosaccharides with one or more sialic acid moieties, which give gangliosides a net negative charge (Figure 10–16). The most abundant of the more than 40 different gangliosides that have been identified are in the plasma membrane of nerve cells, where gangliosides constitute 5–10% of the total lipid mass; they are also found in much smaller quantities in other cell types.
Hints as to the functions of glycolipids come from their localization. In the plasma membrane of epithelial cells, for example, glycolipids are confined to the exposed apical surface, where they may help to protect the membrane against the harsh conditions frequently found there (such as low pH and high concentrations of degradative enzymes). Charged glycolipids, such as gangliosides, may be important because of their electrical effects: their presence alters the electrical field across the membrane and the concentrations of ions—especially Ca2+—at the membrane surface. Glycolipids also function in cell-recognition processes,
Figure 10–16 Glycolipid molecules.
(A) galactocerebroside is called a neutral glycolipid because the sugar that forms its head group is uncharged. (B) A ganglioside always contains one or more negatively charged sialic acid moiety. there are various types of sialic acid; in human cells, it is mostly N-acetylneuraminic acid, or nAnA), whose structure is shown in (c). Whereas in bacteria and plants almost all glycolipids are derived from glycerol, as are most phospholipids, in animal cells almost all glycolipids are based on sphingosine, as is the case for sphingomyelin (see Figure 10–3). gal = galactose; glc = glucose, galnAc = N-acetylgalactosamine; these three sugars are uncharged.
in which membrane-bound carbohydrate-binding proteins (lectins) bind to the sugar groups on both glycolipids and glycoproteins in the process of cell–cell adhesion (discussed in Chapter 19). Mutant mice that are deficient in all of their complex gangliosides show abnormalities in the nervous system, including axonal degeneration and reduced myelination.