Glycosphingolipids erythrocyte membrane

Fig. 11.—Sequence of a 2S-Sugar Residue Glycosphingolipid Isolated from Rabbit Erythrocyte Membranes. (Cleavage points, and the masses of fragment ions of the permethylated derivative, are shown. No fragment-ions were observed above 4000, because of the poor sensitivity at high mass.)...

In addition to the cerebrosides, which contain only one carbohydrate residue, there are other glycosphingolipids in mammalian cells that contain more than one sugar component. These oligosaccharide derivatives are called globosides. For example, lactosyl ceramide (1-O-lactosyl-A acylsphingosine) is a constituent of the erythrocyte membrane. Ceramide trihexoside accumulates in the kidneys of patients with Fabry s disease, due to the lack of a lysosomal a-galactosidase A activity. 

The membrane constituents are lipids (phospholipids, glycosphingolipids, and cholesterol Figure 10-5), carbohydrates, and proteins. The ratio of protein lipid carbohydrate on a weight basis varies considerably from membrane to membrane. For example, the human erythrocyte membrane has a ratio of about 49 43 8, whereas myelin has a ratio of 18 79 3. The composition of the normal human erythrocyte membrane is shown in Table 10-2. All membrane lipids are amphipathic (i.e., polar lipids). The polar heads of the phospholipids may be neutral, anionic, or dipolar. The surface of the membrane bears a net negative charge. The distribution of lipid constituents in the bilayer is asymmetrical. For example, in the erythrocyte membrane, phosphatidylethanolamine and phosphatidylserine are located primarily in the internal monolayer, whereas phosphatidylcholine and sphingomyelin are located in the external monolayer. 

The five major neutral glycosphingolipids of human plasma have been characterized and each has a structure which has been identified previously. One of these glycolipids, D-glucosylceramide, and possibly a second, lactosyl ceramide, exchange between plasma and erythrocyte pools. The conclusion is drawn in terms of the relative roles of carbohydrate and lipid moieties of the glycosphingolipids in maintaining that association with erythrocyte membranes. 

Applications of fast atom bombardment (FAB)-m.s. and laser desorption-m.s. in the analysis of complex human milk oligosaccharides, phosphoinositol-linked glycans from surface glycoproteins, and high molecular weight glycosphingolipids (with up to 40 sugar residues) present in rabbit erythrocyte membranes, have been reviewed (45 refs.). ... 

In most cases the exact location of glycosphingolipid bios5uithesis has not been established. Synaptosomes, pinched ofiF nerve endings, were shown to be rich in glycosyl transferases (Hildebrand et al., 1970 Den and Kaufman, 1968). Studies of Dawson and Sweeley (1970) led to the conclusion that the glycosphingolipids belonging to series II (see Fig. 1) of the erythrocyte membrane—with the exception of Glc-Cer—are synthesized in the bone marrow and do not exchange with their counterparts in the plasma. On the contrary, the Glc-Cer of red cells, which is not synthesized in the bone marrow, is... 

Glycosphingolipids or cerebrosides, which are ceramides with the terminal hydroxyl linked by a glycosidic bond to a sugar moiety, can be handled by MS and GC-MS [285]. Among the sources of glycosphingolipids, characterised with the help of MS, are the membranes of human erythrocytes [300], CSF [301] and from the pancreas of a patient with Fabry s disease [302]. 

Phospholipids and glycosphingolipids are amphipathic lipid constituents of membranes (Chapter 10). They play an essential role in the synthesis of plasma lipoproteins (Chapter 20) and eicosanoids (Chapter 18). They function in transduction of messages from cell surface receptors to second messengers that control cellular processes (Chapter 30) and as surfactants. Cholesterol is mainly of animal origin and is an essential constituent of biomembranes (Chapter 10). In plasma, cholesterol is associated with lipoproteins (Chapter 20). Cholesterol is a precursor of bile acids formed in the liver of steroid hormones secreted by adrenals, gonads, and placenta and 7-dehydrocholesterol of vitamin D formed in the skin. In tissues, cholesterol exists primarily in the unesterified form (e.g., brain and erythrocytes), although appreciable quantities are esterified with fatty acids in liver, skin, adrenal cortex, and plasma lipoproteins. 

Bidirectional transporters. The bidirectional transporters at the plasma membrane randomize the lipid distribution across the plane of the bilayer, and are commonly referred to as scramblases [17]. The action of scramblase is summarized in Fig. 5, and is similar to that of the previously described transbilayer transporter present in the ER. Scramblase protein was first functionally identified in erythrocytes but is also present in nucleated cells. The scramblase shows no lipid specificity and essentially collapses the asymmetry of lipids at the cell surface. Phospholipids, SM, and glycosphingolipids all serve as substrates. The randomizing function of the plasma membrane protein is activated by Ca " and does not require ATP. 

Flammache D, Yahi N, Maresca M, Pieroni G, Fanlini J. Human erythrocyte glycosphingolipids as alternative cofactors for human immunodeficiency virus type 1 (HIV-1) entry evidence for CD4-induced interactions between HIV-1 gpl20 and reconstituted membrane microdomains of glycosphingolipids (Gb3 and GM3). / Vird. 1999 73(6) 5244r-5248. 

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