Cholesterol skeletons

Cholesterol esters form crystalline structures that are similar to those formed by other lipids, consisting of alternating infinite lamellae, so that the hydrocarbon chains form close-packed sheets segregated from layers of cholesterol skeletons. There are three t) s of such structures [6]. One such can be represented by the chiral molecule cholesterol oleate, where pairs of cholesterol skeletons are arranged in an antiparallel packing in one layer, with the hydrocarbon chains in the adjacent layer. The cross-sectional area of the cholesterol molecule is about 40 A2 (derived from pressure-area monolayer curves), corresponding to the cross-sectional area of two hydrocarbon chains. The chains therefore form an interpenetrating layer. 

However, there is a structure consistent with both the required space group and the optical properties. The gyroid surface, which occurs frequently in lipid-water systems, provides such a possibility. If we assume that cholesterol skeletons form rod-like infinite helices, this structure represents an effective three-dimensional packing of such helices. Thus, the rods form a body-centered arrangement as shown in Fig. 5.5. In this structure, there is a helical twist between the rods, in addition to the cholesteric twist within each rod. The h)rperbolic structure is a consequence of the chirality of the esters, which induces torsion into the packing arrangement. A racemic mixture does not exhibit this phase natural cholesteric esters contain a single enantiomer only. 

Figure 5.5 Model of the packing of helical rods of cholesterol skeletons according to fire geometry defined by the gyroid. The three rod-directions are parallel to the [lll]-directions, and one set of rods is perpendicular to the plane of the figure.

The basic cholesterol skeleton can also be modified by the incorporation of a nitrogen heteroatom as in the steroidal alkaloids. Two examples are abutilosides A and B (66 and 67) isolated from S. abutiloides [68-70], which are closely related to the open-chain steroidal glycosides abutilosides D-G (47-50) [45] discussed above. Glycosteroidalkaloids such as these are particularly abiuidant in the Solanum (Solanaceae) [68-70], Lycopersicon (Solanaceae) [71-73], and Fritillaria (Liliaceae) [74—76]. 

James et al. synthesized a new gelator by combining a boronic acid moiety with the cholesterol skeleton (cholesterylphenylboronic acid 1). It was found that saccharide complexes of 1 efficiently gelatinize several organic solvents. The gelation properties such as the sol-gel phase transition... 

Cholesterol is an important constituent of the mammalian cell membrane and is a frequently used component of liposomal formulations in drug-delivery technology. Numerous cholesterol derivatives containing boron cluster attached to the cholesterol skeleton as external entities have been synthesized as potential boron carriers for BNCT. In general, two types of cholesterol boron cluster... 

Cholesterol was isolated m the eighteenth century but its structure is so complex that Its correct constitution was not determined until 1932 and its stereochemistry not verified until 1955 Steroids are characterized by the tetracyclic ring system shown m Figure 26 9a As shown m Figure 26 9b cholesterol contains this tetracyclic skeleton modified to include an alcohol function at C 3 a double bond at C 5 methyl groups at C 10 and C 13 and a C Hn side chain at C 17 Isoprene units may be discerned m var lous portions of the cholesterol molecule but the overall correspondence with the iso prene rule is far from perfect Indeed cholesterol has only 27 carbon atoms three too few for It to be classed as a tnterpene... 

Bde salts, cholesterol, phosphoHpids, and other minor components are secreted by the Hver. Bile salts serve three significant physiological functions. The hydrophilic carboxylate group, which is attached via an alkyl chain to the hydrophobic steroid skeleton, allows the bile salts to form water-soluble micelles with cholesterol and phosphoHpids in the bile. These micelles assist in the solvation of cholesterol. By solvating cholesterol, bile salts contribute to the homeostatic regulation of the amount of cholesterol in the whole body. Bile salts are also necessary for the intestinal absorption of dietary fats and fat-soluble vitamins (24—26). 

In preclinical models of postmenopausal osteoporosis, lasofoxifene inhibited bone turnover and prevented bone loss throughout the skeleton (Maeda et al. 2004). The primary indication of lasofoxifene is the treatment and prevention of postmenopausal osteoporosis. In preclinical models, lasofoxifene inhibited breast tumor formation and reduced serum cholesterol (Maeda et al. 2004). Lasofoxifene-treated animals did not differ from ovariectomized controls with respect to endometrial thickness and superficial and basal endometrial gladular epithelial luminal area (Maeda et al. 2004 Ke et al. 2004). 

Steroids, compounds with a cyclopenta[a]phenanthrene skeleton (15), include a wide range of natural products such as sterols (e.g., cholesterol), sex hormones, adrenocorticoid hormones, cardiac glycosides and vitamin D [31]. Sterols are steroids having a hydroxyl group at position 3 of the basic skeleton. Steroids can be found both in plants and in animals. 

Cholesterol is derived from the steroid skeleton by adding a hydroxyl group at C3, methyl groups at CIO and C13, an eight-carbon alkyl group at C17, and introducing a double bond between carbon atoms 5 and 6.1 have taken some pains to indicate the stereochemistry at each of the eight chiral centers in this molecule its shape matters. 

Our present ideas about the nature of biological membranes, which are so fundamental to all biochemical processes, are based on the Singer-Nicholson mosaic model. This model of the membrane is based on a phospholipid bilayer that is, however, asymmetrical. In the outside monolayer, phosphatidylcholine (lecithin) predominates, whereas the inner monolayer on the cytoplasmic side is rich in a mixture of phos-phatidylethanolamine, phosphatidylserine, and phosphatidylinositol. Cholesterol molecules are also inserted into the bilayer, with their 3-hydroxyl group pointed toward the aqueous side. The hydrophobic fatty acid tails and the steran skeleton of cholesterol... 

The all-tra 5 -squalene (C30H50), discovered in shark liver oil in the 1920s, is a triterpene, but one in which the isoprene rule at violated in one point. Rather than a head-to-tail arrangement of six units of isoprene, there appear to be farnesyl units that have been connected tail to tail. Almost aU steroids are biosynthesized from cholesterol. Cholesterol is biosynthesized from squalene, which is first converted to lanosterol. The conversion of squalene to the steroid skeleton is an oxirane, squalene-2,3-oxide, which is transformed by enzymes into lanosterol, a steroid alcohol naturally found in wool fat. The whole process is highly stereoselective. 

Clinical measurements of total cholesterol in serum or plasma detect cholesterol esters in addition to cholesterol. Between 60 and 70% of the cholesterol transported in blood is in an esterified form, where the /3-3-OH group on the steroid skeleton is covalently linked to a naturally occurring... 

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