Oxysterols structure

There are, as yet, no standard methods for determining oxysterols in food. As a conseqnence, considerable variations in cholesterol oxide levels in similar kinds of foods have been reported by varions laboratories (Dutta et al., 1999). For quantification of oxysterols in samples, the nse of an internal standard technique is recommended. For oxysterol separation, capillary columns with a nonpolar stationary phase are most often nsed. For confirmation of oxysterol structure, the use of gas chromatography/mass spectrometry (GC/MS) is highly recommended. During analytical procednres, serious attention must be paid to the possibility of artifacts of oxysterols from cholesterol. In 1992, Wasilchuk et al. developed a procedure for detecting artifactual generation of oxysterols using [ Hg] cholesterol as an internal standard. 

Janowski, B.A., Grogan, M.J., Jones, S.A., Wisely, G.B., Kliewer, S.A., Corey, E.J. and Mangelsdorf, D.J. (1999) Structural requirements of ligands for the oxysterol liver X receptors LXRa and LXRp. Proceedings of the National Academy of Sciences of the United States of America, 96, 266-271. 

Wu Z, Martin KO, Javitt NB, Chiang JY. 1999. Structure and functions of human oxysterol 7alpha-hydroxylase cDNAs and gene CYP7BL J Lipid Res 40 2195-2203. 

Cholesterol is an important structural component of cellular membranes, where it plays a role in modulating membrane fluidity and phase transitions, and, together with sphingomyelin, forms lipid rafts or caveolae, which are sites where proteins involved in diverse signaling pathways become concentrated. Furthermore, cholesterol is a precursor of oxysterols, steroid hormones, and bile acids. 

That the effect of BR is not simply due to the "oxidized" sterol structure is supported by our observation that oxysterols, which are strong inhibitors in mammalian cell cultures, were nearly inactive in our system. Again this points to... 

Oxysterols arise from dietary sources, non-enzymatic oxidation, and enzymatic oxidation reactions [19]. The structure of some of the oxysterols that may be involved in atherosclerosis are shown in Fig. 5. Dietary oxysterols are incorporated into chylomicrons and... 

Fig. 5. Structures of some oxysterols that have been implicated in atherogenesis. Adapted from Ref. [19]. Reproduced with permission from the publisher.

Unlike the steroid receptors, most of which function as homodimers, a second class of NRs function as heterodimers with the retinoid X receptor (RXR). Importantly, these receptors serve as sensors for metabolites such as fatty acids, oxysterols, and bile acids. Key elements of ligand recognition and receptor activation have been elucidated following structure-function analyses of several receptors in this family including the PPARs, liver X receptors (LXRs), and FXR. 

The expression cholesterol oxidation products (COP) or oxysterols refers to a group of sterols similar in structure to cholesterol but containing an additional hydroxyl, ketone, or epoxide group, on the sterol nucleus or a hydroxyl group on the side chain of the molecule. Table 6.2 presents the names of most prominent COP formed in foods, plasma, and tissues. 

When analysis is performed on ion-trap instruments, this ion can be selected and subjected to further fragmentation. The resulting MS spectra are rich in structural information (Figure 2.15). The MS/MS spectra on tandem quadrupole or Q-TOF instruments are effectively a composite of MS2 and MS3 spectra recorded on an ion trap. Using our charge-tagging methodology, we have profiled the oxysterol content of adult, newborn, and... 

On this basis, a versatile even if contradictory role of oxysterols may emerge, which poses the question of how they actually affect the atherosclerotic lesion development and which factors might modulate their behavior. In this connection, how much does it depend on the nature of oxysterols thanselves (e.g., chemical structure, enzymatic or nonenzymatic origin) and how much on extrinsic factors (e.g., stage of disease progression, cell phenotype, presence of other bioactive compounds) ... 

Sevanian et al. (1994) applied GLC and LC/TS/MS for the analysis of plasma cholesterol-7-hydroperoxides and 7-ketocholesterol. Analysis of human and rabbit plasma identified the commonly occurring oxidation products, yet dramatic increases in 7-ketocholesterol and cholesterol-5p, 6P-epoxide were observed. The study failed to reveal the presence of choles-terol-7-hydroperoxides, which were either too unstable for isolation, metabolized or further decomposed. The principal ions of cholesterol oxides monitored by LC/TS/MS were m/z 438 (cholestane triol) m/z 401 (cholesterol-7-hydroperoxide) m/z 401 (7-ketocholesterol) m/z 367 (7a-hydroxycholesterol) m/z 399 (cholesta-3,5-dien-7-one) and m/z 385 (choles-terol-5a,6a-epoxide). The major ions were supported by minor ions consistent with the steroid structure. Kamido et al. (1992a, b) synthesized the cholesteryl 5-oxovaleroyl and 9-oxononanoyl esters as stable secondary oxidation products of cholesteryl arachidonate and linoleate, respectively. These compounds were identified as the 3,5-dinitrophenylhydrazone (DNPH) derivatives by reversed-phase LC/NICI/MS. These standards were used to identify cholesteryl and 7-ketocholesteryl 5-oxovaleroyl and 9-oxononanoyl esters as major components of the cholesteryl ester core aldehydes generated by copper-catalysed peroxidation of low-density lipoprotein (LDL). In addition to 9-oxoalkanoate (major product), minor amounts of the 8, 9, 10, 11 and 12 oxo-alkanoates were also identified among the peroxidation products of cholesteryl linoleate. Peroxidation of cholesteryl arachidonate yielded the 4, 6, 7, 8, 9 and 10 oxo-alkanoates of cholesterol as minor products. The oxysterols resulting from the peroxidation of the steroid ring were mainly 7-keto, 7a-hydroxy and 7P-... 

Possible structures of bile alcohol (oxysterol) conjugates found in plasma of a child with neonatal hepatitis of unknown etiology. The location of the hydroxyl groups and conjugating groups are not known however, previous studies of children have shown sulfation... 

Sterols are a class of lipids containing a common steroid core of a fused four-ring structure with a hydrocarbon side chain and an alcohol group. Cholesterol is the primary sterol lipid in mammals and is an important constituent of cellular membranes. Oxidization and/or metabolism of cholesterol yield numerous oxysterols, steroids, bile acids, etc., many of which are important signaling molecules in biological systems. Cholesteryl esters esterified with a variety of fatty acyls are enriched in... 

---