Cerebrosides, structure

Cerebroside Structure and Metabolism. The structure of cerebrosides is particularly important because it has been claimed that those that accumulate in Gaucher s disease are abnormal. The general formula of cerebrosides includes equimolecular amounts of hexose, sphingosine, and fatty acids. 

Sphingoplasmalogens, a new class of glycolipids recently described by Kochetkov et al. (1963, 1964), contains a vinyl ether (at carbon 3 of the sphingosine) in a cerebroside structure ... 

Cerebrosides are found in the brain and in the myelin sheath of nerve tissue The structure of the cerebroside phrenosine is... 

FIGURE 8.13 The structure of a cerebroside. Note the sphiugosiue backbone. 

The glycosphingolipids (GSLs) are sugar-containing lipids built on a backbone of ceramide they include galactosyl- and glucosylceramide (cerebrosides) and the gangliosides. Their structures are described in Chapter 14. They are mainly located in the plasma membranes of cells. 

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. 

Fig. 9.5 Chemical structures of elicitors from Leptosphaeria maculans isolate virulent on canola produced in minimal medium cerebrosides C (13) and D (14)...

Hydrophobic and Hydrophilic Components of Membrane Lipids A common structural feature of membrane lipids is their amphipathic nature. For example, in phosphatidylcholine, the two fatty acid chains are hydrophobic and the phosphocholine head group is hydrophilic. For each of the following membrane lipids, name the components that serve as the hydrophobic and hydrophilic units (a) phos-phatidylethanolamine (b) sphingomyelin (c) galactosyl-cerebroside (d) ganglioside (e) cholesterol. 

Kayser, S. G. and Patton, S. 1970. The function of very long chain fatty acids in membrane structure Evidence from milk cerebrosides. Biochem. Biophy. Res. Commun. 41, 1572-1578. 

Raman-spectral studies of cerebrosides in the solid and gel phases have been reported.201 Assignments of frequencies, and comparison of peak heights for characteristic vibrations, allowed elucidation of the conformation of both the chain and head-group portions of these molecules. Interpretation of the spectral data was found in agreement with calorimetric and X-ray structural data. 

From the sponge M. incrustans, two cerebrosides and a polar glycolipid were isolated.78 Both cerebrosides contain galactose and sphingosine, but differ in the nature of their fatty acids the less polar cerebroside contains normal, and the more polar, monohydroxy, acids. The structure of the polar glycolipid was not established, but it was shown to contain sphingosine, fatty acids, galactose, arabinose, fucose, and phosphorus.78... 

From the sea anemone M. senile was isolated j3-glucopyranosyl-( 1 - l)-ceramide, the structure of which was determined by mass spectrometry, H-n.m.r. spectroscopy, and chemical splitting. The major sphingosine in the cerebroside is a new base containing two double bonds and branching at one double bond, namely, 2-amino-D-eryf/jro-l,3-dihydroxy-9-methyl-( , E)-octadeca-4,8-diene. The major fatty acids are Ci6 0 and C20 o a-hydroxy acids.133... 

The hepatopancreas of H. schlegelii was found to contain an unusual cerebroside, a mannosylceramide, isolated from the monohexosylceramide fraction by t.l.c. on borate-impregnated silica gel.265 Its structure was shown to be /3-D-mannosylceramide, whose major sphingosine base is 4-sphingenine, and the fatty acids constitute a mixture of normal (77% of the total acids) and a-hydroxy acids, with hexadecanoic acid preponderant (43.7% of the total acids).265... 

Other glycolipids from aquatic invertebrates are also characterized by a great variety of structures. Along with compounds known also to be present in vertebrates (gluco- and galacto-cerebrosides and lactosylceramide), new glycosphingolipids have been detected that differ from the glycosphin-... 

Using the new procedure, attempts were made to quantitate the cerebrosides located on the surface of myelin. Myelin is composed of multilamellar bilayers of membrane of approximately 70% lipid and 30% protein (16). About 20% of the total lipid consists of cerebroside and sulfatide. Because of the lipophilic nature of the ceramide moiety and the hydrophilic nature of galactose, it has been postulated that the galactose moiety of myelin cerebrosides is facing the surface while the ceramide moiety is buried within the bilayer. Even considering the multilamellar structure of myelin, at least several percent of the cerebrosides should be present on the myelin surface. The method described in this manuscript should allow us to determine surface cerebrosides to as little as 0.5% of the total cerebrosides. 

S. B. Levery, M. S. Toledo, R. L. Doong, A. H. Straus, and H. K. Takahashi, Comparative analysis of ceramide structural modification found in fungal cerebrosides by electrospray tandem mass spectrometry with low energy collision-induced dissociation of Li + adduct ions, Rapid Commun. Mass Spectrom., 14 (2000) 551-563. 

The principal routes of penetration are thus transcellular and intercellular. Currently there is considerable debate as to which of these predominates. Work with esters of nicotinic acid has shown that the intercellular channels are significant [5.] and considerable effort is being conducted to identify their exact nature and role. Microscopic examination shows that they contain structured lipids the chemical nature of which is complex [6J. Cholesterol esters, cerebrosides and sphingomyelins are present in association with other lipids in smaller concentrations. It is likely that the main barrier to skin penetration resides in the channels and that a diffusing drug molecule experiences a lipid environment which has considerable structure. Penetration enhancers may act by temporarily altering the nature of the structured lipids, perhaps by lowering their normal phase transition temperature which occurs around 38°C. 

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