Sphingolipids cerebrosides

Sphingolipids (ceramids, sphingomyelin, cerebrosides, sulfatides, gangliosides) and lipids with secondary amines produce blue spots on a white backgound (CAUTION benzidine is a carcinogen)... 

Because membranes components participate in nearly every cell activity their structures are also dynamic and far from the equilibrium states that are most readily understood in biophysical terms. Newly synthesized bilayer lipids are initially associated with endoplasmic reticulum (Ch.3) whereas phospholipids initially insert into the cytoplasmic leaflet while cholesterol and sphingolipids insert into the luminal endoplasmic reticulum (ER) leaflet. Glycosylation of ceramides occurs as they transit the Golgi compartments, forming cerebrosides and gangliosides in the luminal leaflet. Thus, unlike model systems, the leaflets of ER membranes are asymmetric by virtue of their mode of biosynthesis. 

In general the sphingolipids are located on the exterior face of a membrane while the phospholipids make up the inner face. This is understandable when we recall that sphingolipids include the gangliosides and cerebrosides whose polar ends contain carbohydrates or complex carbohydrate derivatives. The large number of chiral centers in carbohydrate molecules offer a complex pattern on the surface of the membrane which can impart a large degree of specificity for a particular cell type. The composition and limited fluidity of the bilayer make the entire membrane asymmetric, that is, different on the inner and outer layers or leaflets. 

FIGURE 21-31 Biosynthesis of sphingolipids. Condensation of palmitoyl-CoA and serine followed by reduction with NADPH yields sphinganine, which is then acylated to N-acylsphinganine (a ceramide). In animals, a double bond (shaded pink) is created by a mixed-function oxidase, before the final addition of a head group phosphatidylcholine, to form sphingomyelin glucose, to form a cerebroside. 

A quantitative HPLC method for the analysis of sphingolipids as their perbenzoyl derivatives was first developed for ceramides (5). Ceramides can be conveniently derivatized with benzoic anhydride in pyridine (3 hrs at 110°C) and the products formed have been utilized for the quantitative analysis of NFA and HFA ceramides in normal and Farber s disease tissue. Iwamori and Moser also utilized this procedure for the analysis of ceramides in Farber s disease urine (6). More recently Iwamori and Moser (7) established that the ceramide derivatives formed by reaction with benzoyl chloride or benzoic anhydride are analogous to those formed with cerebrosides. They also characterized the behavior... 

Our new method of sphingolipid analysis using high performance liquid chromatography allows us to determine not only their quantities but also their homolog compositions in a small amount of tissue. We now feel that less than 1 mg of fresh brain or nerve tissue is sufficient for complete analysis. The application of this new method for analyzing cerebroside and sulfatide-in plaques of brain from a patient with multiple sclerosis has been recently described (15). 

Lipids are far more diverse chemically than other typical biomolecules such as amino acids, carbohydrates, and nucleotides. The definition of lipids includes simple fatty acids and their glycerol esters, sterols such as cholesterol, and phospholipids, sphingolipids, and cerebrosides. Lipids are generally defined by their common hydrophobic character, which makes them soluble in organic solvents such as chloroform. Virtually all lipids also have a hydrophilic group, which makes them surface active. 

Certain spray reagents can be helpful in locating these carbohydrate-containing sphingolipids. Resorcinol yields a blue violet color with gangliosides, and naphthol produces a blue color with cerebrosides, cerebroside sulfuric acids, and gangliosides. 

Sphingolipids are not essential nutrients but are increasingly being recognized as important in nutrition, as was reviewed by Vesper et al. (1999). In mammalian tissues and milk, the sphingolipids include ceramides, sphingomyelins, cerebrosides, gangliosides and sulfatides. 

Sphingolipids comprise glycolipids (gangliosides and cerebrosides) and the phospholipid, sphingomyelin. These compounds, too, are important membrane constituents. The biosynthesis of sphingolipids involves the common intermediate ceramide (Fig. 13-15). 

Pascher I, Sundell S (1977) Molecular arrangements in sphingolipids. The crystal structure of cerebroside. Chem Phys Lipids 20 175-191... 

SPHINGOLIPIDS AND OTHER LIPIDS Phytosphingolipids Cerebroside Phytosphingosine Sulfolipids... 

Pascher, I., and S. Sundell, Molecular Arrangements in Sphingolipids. The Crystal Structure of Cerebroside, Chem. Phys. Lipids 20 175-191 (1977). 

Glycolipids (or sphingolipids) are derived from the lipid sphingosine (see Figure 6-15). This class of compounds includes cerebrosides and gangliosides. Some bacterial toxins and viruses use them as receptors. 

Xu X, Bittman R, Duportail G, et al. (2001) Effect of the structure of natural sterols and sphingolipids on the formation of ordered sphingolipid/sterol domains (rafts). Comparison of cholesterol to plant, fungal, and disease-associated sterols and comparison of sphingomyelin, cerebrosides, and ceramide. J Biol Chem 276 33540-33546... 

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