Ester cerebrosides

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. 

Arylsulfatase cleaves sulfate esters. Cerebroside sulfate is its natural substrate. The enzyme is also active toward p-nitrocatechol sulfate, which is the basis for this assay. 

EC 3.1.6.1) is a lysosomal enzyme that hydrolyzes sulfuric acid ester bonds. The enzyme exists in two forms, arylsulfatases A and B, that differ in substrate specificity and in sensitivity toward inhibitors [142][143]. Human tissues contain more arylsulfatase A than arylsulfatase B. The natural substrates of these enzymes are complex lipids such as cerebroside 3-sulfate, and gly-cosaminoglycans such as chondroitin 4-sulfate and derman sulfate [144], Deficiencies of these enzymes are associated with a number of lysosomal disorders. 

Glycolipids are important constituents of the plasma membranes, of the endoplasmic reticulum, and of chloroplasts. The cerebrosides and their sulfate esters, the sulfatides, are especially abundant in myelin. In plant membranes, the predominant lipids are the galactosyl diglycerides.29 74 The previously described ether phospholipids (archaebacteria), ceramide arnino-ethylphosphonate (invertebrates), and sulfolipid (chloroplasts) are also important membrane components. 

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. 

The composition of milkfat is somewhat complex. Although dominated by triglycerides, which constitute some 98% of milkfat (with small amounts of diglycerides, monoglycerides, and free fatty acids), various other lipid classes are also present in measurable amounts. It is estimated that about 500 separate fatty acids have been detected in milk lipids it is probable that additional fatty acids remain to be identified. Of these, about 20 are major components the remainder are minor and occur in small or trace quantities (4, 5). The other components include phospholipids, cerebrosides, and sterols (cholesterol and cholesterol esters). Small amounts of fat-soluble vitamins (mainly A, D, and E), antioxidants (tocopherol), pigments (carotene), and flavor components (lactones, aldehydes, and ketones) are also present. 

Sphyngophosphoaminolipides, in which the alcohol is sphingosine (sphingomyeline). Cerebrosides not possessing an ester linkage are not included in the lipide group but in that of the heterosides. 

Neutral glycosphingolipids (for example, zoo- and phyto-cere-brosides, diglycosylceramides, esters of cerebrosides with fatty acids, sphingoplasmogens, and gangliosides free from neuraminic acid). 

Klenk and Lohr81 have reported the isolation of cerebroside esters from human-brain material. One hydroxyl group of the D-galactosyl group, or of the sphingosine residue, is in covalent conjugation with long-chain fatty acids. 

Hydroxy FA occnr in both satnrated and nnsatnrated forms, with varions positional isomers. There are three major types. First, the 2-hydroxy (2-OH) or a-hydroxy FA (Fignre 3.1). These satnrated components occnr as a series of even nnmbered acids from Cm to C26 and are components of animal tissnes (within cerebrosides) and certain plants. Second, 3-hydroxy (3-OH) or P-hydroxy FA exist as a series of even-nnmbered acids from Cm to C. They are ubiquitous components of many bacteria and yeasts, where they exist as ester-linked residues of extracellular lipids. Third, the hydroxyl group may be present at the penultimate carbon from the carboxyl group (i.e., co2, or otherwise referred to as co-1) of the chain series Cn to Cm- In most instances, these compounds represent intermediates in the co-oxidation of FA by microorganisms. 

Hydroxyfatty adds. Fatty acids containing an OH function. In plants H. a, occur mainly as esters, e. g., in triglycerides (ricinus oil) and waxes (e.g., camauba and beeswax). In plants and animals 2-H. are components of cerebrosides. On the other hand, esters and glycosides of 3-H. [e.g. (R)-3-hydroxypalmitic acid from Rhodotorula yeasts, C gH3203, Mr 272.43, mp. 78 - 79 °C, [a]o -12.9°] are typical components of bac-... 

Yamakawa, T., Kiso, N., Handa, S., Makita, A. Yokoyama, S. (1962) On the Structure of Brain Cerebroside Sulfuric Ester and Ceramide Dihexoside of Erythrocytes , Journal of Biochemistry (Tokyo), 52, 226-7... 

Methanolysis of a cerebroside with 1 M HCl in 82% aqueous methanol, according to the method of Gaver and Sweeley [29], yields a mixture of the fatty acid methyl ester (FAME) and the IrMig-chain base together with the methyl glycoside of the monosaccharide unit (Scheme 2). 

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