Sphingolipids

Sphingolipids are found in the membranes in animals, plants, and some lower forms of life but are absent from most bacteria such as E. coli. The common structural feature of all sphingolipids is a long-chain hydroxylated secondary amine (see fig. 17.4). Sphingolipids are particularly abundant in myelin sheath, a multilayered membranous structure that protects and insulates nerve fibers. Recently several sphingolipids have been implicated as second messengers in cells. 

Sphingolipids were first described in a remarkable treatise on the chemical constitution of the brain by Johann L. W. Thudichum, a physician-scientist in London, who published his findings more than 100 years ago. A major impetus for the study of the chemistry and metabolism of the sphingolipids was the discovery of several rare human diseases that could be attributed to the abnormal accumulation of sphingolipids. This accumulation has been shown to result from a defect in catabolism that normally occurs in lysosomes. It is now known that many different kinds of sphingolipids exist, and more than 300 structures have been reported to occur in nature. 

Sphingolipids are built from long-chain, hydroxylated bases rather than from glycerol. Two such bases are found in animals sphingosine and dihydrosphingosine (sphinganine), with the former being much more common. 

Question From which compounds is sphinganine synthesized in living systems  

Notice the polar part is related to the amino acid serine (a) and the nonpolar part resembles palmitate (b). A reaction between these two compounds, with the elimination of C02, is followed by a reduction reaction which yields sphinganine. 

When the amino group of sphingosine or sphinganine is acylated with a fatty acid, the product 

The primary hydroxyl group is substituted in one of two ways to give two classes of sphingolipid these are the phosphosphingolipids and glycosphingolipids. 

Sphingolipids along with sterols and glycerophospholipids are the most abundant class of lipids constituting eukaryotic cellular membranes. 

Their functions have been best studied in the model yeast Saccharomyces cerevisiae. Here, apart from structural functions, they play important roles as second messengers in signal transduction pathways, regulating diverse cellular processes like growth, nutrient uptake, heat stress response, cell wall synthesis 

Sources Naphtha Europe - CMAI Propylene Europe Contract-CMAI Benzene Europe-ICIS Sugar No. 11 - ICE Ethanol (Hydrous) Brazil - Cepea Glucose in Corn (65%) - CBOT. 

Mammalian SC ceramides contain one of four sphingoid bases, namely sphingosine, 6-hydroxysphingosine, phytosphingosine and dihydrosphingosine 

Despite volatility sugar remains a competitive feedstoc 

Sphingolipids contain sphingosine, an amino alcohol with a long unsaturated hydrocarbon chain (D-erythro-1,3-dihydroxy-2-amino-trans-4-octadecene) instead of glycerol  

Sphingolipids which occur in plants, e. g., wheat, contain phytosphingosines  

Sphingophospholipids, Sphingomyelin is one example of a sphingophospholipid. It is the most abundant sphingolipid and is found in myelin, the fatty substance of the sheath around nerve fibers. The structure of sphingomyelin is  

The amino group in sphingolipids is linked to a fatty acid to form a carboxy amide, denoted as ceramide. The primary hydroxyl group is either esterified with phosphoric acid (sphingophospholipid ceramide-phosphate-base) or bound glycosidically to a mono- di-, or oligosaccharide 

Gangliosides contain sialic acid (N-acetyl-neuraminic acid cf. Formula 3.40 b). In the ganglioside fraction of milk monosialosyl-lactosyl-ceramide (cf. Formula 3.41) was identified. 

Cholesterol makes up 95% of the total milk sterols and, because it is associated with the milk fat globule membrane, its content is highly correlated with the total fat content (Jensen, 2002). Only about 10% of the cholesterol in milk is esterified. 

4-dimethylaminoazobenzene-4-sulphonyl chloride (dabsyl-Cl) has recently been described (Rosenfelder et al., 1983). The stationary phase used was a Zorbax CN column (Du Pont Instruments) and the mobile phase used a gradient of acetonitrile-0.0175 M sodium acetate, pH 

Ceramides have been resolved by both reversed phase HPLC and non-aqueous reversed phase HPLC on similar columns. Using an ODS stationary phase in combination with a mobile phase of chloroform-methanol, the benzoyl and p-nitrobenzoyl derivatives of both hydroxy and non-hydroxy ceramides from egg yolk and bovine brain were reported to be resolved (Do et al., 1981). The /7-nitrobenzoyl derivatives were quantitated by UV detection at 260 nm and a lower limit of detection of 50 pmol was reported. An alternative derivatisa- 

The benzoylated derivatives of both hydroxy and non-hydroxy ceramides have been resolved using non-aqueous reversed phase chromatography with a variety of mobile phases including either 0.05% methanol in n-pentane or mixtures of hexane-ethyl acetate (94 6, 95 5, 97 3) (Sugita et al., 1979 Iwamori and Moser, 1975 Iwamori et al., 1979). 

Sphingohpids in tree nuts are given in Chapter 5. They are a class of lipids that are hydrolyzed throughout the gastrointestinal tract into metabolites that include ceramides and sphingoid bases 

Tree Nuts Composition, Phytochemicais, and Heaith Effects 

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We turn now to the biosynthesis of lipid structures. We begin with a discussion of the biosynthesis of fatty acids, stressing the basic pathways, additional means of elongation, mechanisms for the introduction of double bonds, and regulation of fatty acid synthesis. Sections then follow on the biosynthesis of glyc-erophospholipids, sphingolipids, eicosanoids, and cholesterol. The transport of lipids through the body in lipoprotein complexes is described, and the chapter closes with discussions of the biosynthesis of bile salts and steroid hormones. 

FIGURE 25.25 Biosynthesis of sphingolipids in animals begins with the 3-ketosphinga-nine synthase reaction, a PLP-dependent condensation of palmitoyl-CoA and serine. Subsequent rednction of the keto group, acylation, and desatnration (via rednction of an electron acceptor, X) form ceramide, the precnrsor of other sphingolipids. 

Phospholipids Sphingolipids Are Involved in Multiple Sclerosis and Lipidoses... 

In multiple sclerosis, which is a demyelinating disease, there is loss of both phospholipids (particularly ethanolamine plasmalogen) and of sphingolipids from white matter. Thus, the lipid composition of white matter resembles that of gray matter. The cerebrospinal fluid shows raised phospholipid levels. 

Phospholipids and sphingolipids are involved in several disease processes, including respiratory distress syndrome (lack of lung surfactant), multiple sclerosis... 

Merrill AH, Sweeley CC Sphingolipids metabolism and cell signaling. In Biochemistry of Lipids, Lipoproteins and Membranes. Vance DE, Vance JE (editors). Elsevier, 1996. 

While the fluid mosaic model of membrane stmcture has stood up well to detailed scrutiny, additional features of membrane structure and function are constantly emerging. Two structures of particular current interest, located in surface membranes, are tipid rafts and caveolae. The former are dynamic areas of the exo-plasmic leaflet of the lipid bilayer enriched in cholesterol and sphingolipids they are involved in signal transduction and possibly other processes. Caveolae may derive from lipid rafts. Many if not all of them contain the protein caveolin-1, which may be involved in their formation from rafts. Caveolae are observable by electron microscopy as flask-shaped indentations of the cell membrane. Proteins detected in caveolae include various components of the signal-transduction system (eg, the insutin receptor and some G proteins), the folate receptor, and endothetial nitric oxide synthase (eNOS). Caveolae and lipid rafts are active areas of research, and ideas concerning them and their possible roles in various diseases are rapidly evolving. 

Fig. 14.—Schematic Representation of the Fragmentation Observed in the Positive F.a.b.-Mass Spectrum of a Permethylated Ganglioside Isolated from Granulocytes. [Other glyco-sphingolipids fragment in a similar way. Major cleavages are shown with solid lines, and minor cleavages with dotted lines. The masses of ions resulting from cleavages (a), (b), and (c) define the type of sphingosine and the type of fatty acid. In this example, (a) is 548, (b) is [M + H] minus 238, and (c) is [M + H] minus 533.]...

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

Haidar, K. Sphingolipid synthesis and membrane formation by Plasmodium. Tr. Cell Biol. 1996, 6, 398 05. 

Rasmussen JAM, Hermetter A (2008) Chemical synthesis of fluorescent glycero- and sphingolipids. Prog Lipid Res 47 436-460... 

Compound lipids (phospholipids, sphingolipids, glycolipids, and cholesterol and its esters) that make part of the biomembrane are subject to a less active renew-al as compared with triacylglycerides. Their renewal is associated either with the restoration of an impaired portion of the membrane, or with the replacement of a defective molecule by a new one. 

Volume 311. Sphingolipid Metabolism and Cell Signaling (Part A)... 

Marine sponges have long been recognized as a source of novel lipids including unique branched and elongated fatty acids, often found incorporated into phospholipids, triglycerides, and sphingolipids [20-23]. 

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