Cholesterol sulfate ester

The body contains sulfate esters of cholesterol and other sterols,245 sometimes in quite high concentrations relative to those of unesterified steroids. These esters are presumably soluble transport forms. They... 

The ability of insect sulfotransferases to catalyze the sulfation of plant and insect steroids may simply reflect the broad substrate specificity of the enzymes. On the other hand, it may be indicative of a more important physiological function of the enzymes. Sulfate esters of cholesterol, campesterol and e-sitosterol have been identified in the meconium of tobacco hornworm (M. sexta) pupae ( ), and these steroids are known precursors of a-and e-ecdysone and other molting hormones in this species ( ). Further, there is evidence that houseflies (M. domestica) and diapausing pupae of M. sexta convert 22,25 bisdeoxyecdysone, a-ecdysone and 20-hydroxyecdysone into sulfate and glucoside conjugates ( ). 

The blood and tissues of animals typically contain not only unesterified cholesterol (UC), but also cholesterol esters (CE). Most of the CE are formed from long-chain fatty acids such as palmitic acid, oleic acid, linoleic acid, or arachidonic acid, but small amounts of cholesterol sulfate (CS) and cholesterol glucuronide also are present. The aim of this chapter is to provide a brief overview of the biochemistry, physiology, and pathology of these esters as an introduction to the field of CE research. The primary focus will be on long-chain fatty acid esters because much more is known about them than about other CE. However, current knowledge of the biochemistry of CS will be reviewed as well. 

Here cholesterol forms the hydrophobic tail of the surfactant and is attached via a spacer to a hydrophilic pyridinium sulfate ester head. The effect of molecular imprinting in these particles was elegantly demonstrated by an immunoprecipita-tion experiment, in which a,co-cholesterol-functionalized poly(ethylene oxide) was mixed with a suspension of the imprinted particles which led to bridging flocculation and precipitation. 

FIGURE 14.7 Derivatization for ESI-MS/MS. (A) Preparation of the dimethylaminoethylester of dihydroxycholestanoic acid bis acetate. (B) Preparation of aminoethanesulfonate derivative of chenodeoxycholic acid. (C) Formation of sulfate ester of cholesterol. (D) Preparation of oxime of testosterone. 

Cholesterol Cholesterol esters Cholesterol sulfate Triglycerides... 

Modulation of epidermal lipid biosynthesis has been reported to boost drag delivery. It has also been suggested that it is both the hydrophobic nature of the lipids as well as their tortuous, extracellular localization that are responsible for the restriction in the transport of most molecules across the stratum comeum. The function of this barrier depends on three key lipids cholesterol, fatty acid, or ceramides. Delays of synthesis ceramides in the epidermis have been reported as means of barrier perturbation. Inhibitors of lipid synthesis were used to enhance the trans-A cmaV dehvery of hdocaine or caffeine. Alteration of barrier function was produced by the fatty acid synthesis inhibitor S-(tetradecyloxy)-2-furancarboxylic acid, the cholesterol synthesis inhibitor fluvastatin, or the cholesterol sulfate, which resulted in a further increase in lidocaine absorption (38). The major components of sebaceous lipids in the skin are 45-60% TAGs, 25% wax and sterol esters, 12-15% squalene and 10% free fatty acids (39). Some fatty acids, especially unsaturated fatty acids, are well-known skin penetration enhancers. The addition of PC to dermal dosage forms has been reported to increase percutaneous absorption. Lipid disperse systems (LDSs) containing polar lipids, such as PC and glycosylceramide, are also useful for... 

Jetten, A.M., M.A. George, G.R. Pettit, C.L. Herald, and J.I. Rearick Action of Phorbol Esters, Bryostatins, and Retinoic Acid on Cholesterol Sulfate Synthesis Relation to the Multistep Process of Differentiation in Human Epidermal Keratino-cytes. J. Invest. Dermatol. 93, 108 (1989). 

Vineland, NJ) or over-the-counter cosmetic creams promoted for improved hydration (L Oreal, Paris and Dior, Paris). More recently, parenteral liposome formulations of amphotericin B, doxorubicin, and dau-norubicin have been approved and marketed (ABELCET, Elan, the Liposome Co., Inc, Princeton, NJ AmBisome and DaunoXome, Nexstar/Fujisawa, Deerfield Park, IL Amphotec and Doxil, Sequus/ Alza, Menlo Park, CA), with others on the horizon for applications in photodynamic therapy. Although the vast majority of liposome preparations are constructed from phospholipids, other nonphospholipid materials can be used either alone or in mixtures to form bilayer arrays. One such example is Amphotec, which utilizes sodium cholesteryl sulfate as the primary lipid. Other liposome forming materials may include but are not limited to fatty-acid compositions, ionized fatty acids, or fatty acyl amino acids, longchain fatty alcohols plus surfactants, ionized lysophospholipids or combinations, non-ionic or ionic surfactants and amphiphiles, alkyl maltosides, a-tocopherol esters, cholesterol esters, polyoxyethylene alkyl ethers, sorbitan alkyl esters, and polymerized phospholipid compositions. ° ... 

The stratum corneum intercellular lipids exist as a continuous lipid phase occupying about 20% of the stratum corneum volume and arranged in multiple lamellar structures. They are composed of cholesterol (27 /o) and ceramides (41 /o), together with free fatty acids (9 /o), cholesteryl esters (10 /o) and cholesteryl sulfate (2 /o) (Table 1). Phospholipids, which dominate in the basal layer, are converted to glucosylceramides and subsequently to ceramides and free fatty acids, and are virtually absent in the outer layers of the stratum corneum. Eight classes of ceramides have been isolated and identified in human stratum corneum but the functions of the individual ceramide types are not fully understood. Similarly, the exact function of cholesterol esters within the stratum corneum lamellae is also elusive but it is theoretically possible that cholesterol esters may span adjacent bilayers and serve as additional stabilizing moieties. 

A more refined test is the Schultz (1924) method for cholesterol, which involves the application of a mixture of concentrated sulfuric acid and glacial acetic acid to sections which have been oxidized with ferric ammonium sulfate (iron alum). A blue-green color results. The iron alum apparently oxidizes 3-hydroxy steroids and their esters to 7-oxy steroids, which give the Lifschlltz color reaction on the application of the acids. (Fieser and Fieser, 1949, p. 234). This test is considered to be more specific for a limited group of steroids than is the sulfuric acid method cited above, which reveals a large number of unsaturated polycyclic compounds. Recently, however, Kent (1952) has reported that a positive reaction also occurs with carotene. 

A recent abstract and verbal report by McKhann, Levy, and Ho (1965) reports the in vitro synthesis of cerebroside sulfate by a microsomal enzyme system from young rat brain (18— 22 days old). Sonic irradiation of the microsomal fractions resulted in the solublization of a sulfokinase system. The complete synthesis required the microsomal fraction of brain, S04 , ATP, cerebrosides, and a non-ionic detergent (Bbij 96). The reaction reported would be consistant with equations 8, 9, and 10. No incorporation of S-sulfate into a cholesterol ester nor an exchange with unlabelled cerebroside sulfate was observed. 

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