[1] A comparison of methods for the identification of sterols

Nes, William R.

doi:10.1016/s0076-6879(85)11003-7

Cited by 31 publications

(11 citation statements)

References 83 publications

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“…The ions monitored using full scan electron ionization (70 eV) corresponded to the molecular ions of the trimethylsilyl derivatives. Retention times of detectable precursor sterols relative to that of cholesterol were cholestanol (dihydrocholesterol), 1.03; 8-dehydrocholesterol, 1.06; desmosterol, 1.07; 7-dehydrocholesterol, 1.07; lathosterol, 1.10; 4-methylsterol, 1.20; 4,4-dimethylsterol, 1.20; lanosterol, 1.42; and dihydrolanosterol, 1.42, similar to those previously reported for C-3 hydroxylderivatized sterols (17,18).…”

Section: Measurement Of Liver and Plasma Precursor Sterols By Gas Chrsupporting

confidence: 86%

Dual-action hypoglycemic and hypocholesterolemic agents that inhibit glycogen phosphorylase and lanosterol demethylase

Harwood

Petras

Hoover

et al. 2005

Journal of Lipid Research

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Diabetic dyslipidemia requires simultaneous treatment with hypoglycemic agents and lipid-modulating drugs. We recently described glycogen phosphorylase inhibitors that reduce glycogenolysis in cells and lower plasma glucose in ob/ob mice ( J. Med. Chem. , 41: 2934, 1998). In evaluating the series prototype, CP-320626, in dogs, up to 90% reduction in plasma cholesterol was noted after 2 week treatment. Cholesterol reductions were also noted in ob/ob mice and in rats. In HepG2 cells, CP-320626 acutely and dose-dependently inhibited cholesterolgenesis without affecting fatty acid synthesis. Inhibition occurred together with a dose-dependent increase in the cholesterol precursor, lanosterol, suggesting that cholesterolgenesis inhibition was due to lanosterol 14 ␣ -demethylase (CYP51) inhibition. In ob/ob mice, acute treatment with CP-320626 resulted in a decrease in hepatic cholesterolgenesis with concomitant lanosterol accumulation, further implicating CYP51 inhibition as the mechanism of cholesterol lowering in these animals. CP-320626 and analogs directly inhibited rhCYP51, and this inhibition was highly correlated with HepG2 cell cholesterolgenesis inhibition ( R 2 ‫؍‬ 0.77). These observations indicate that CP-320626 inhibits cholesterolgenesis via direct inhibition of CYP51, and that this is the mechanism whereby CP-320626 lowers plasma cholesterol in experimental animals. Dual-action glycogenolysis and cholesterolgenesis inhibitors therefore have the potential to favorably affect both the hyperglycemia and the dyslipidemia of type 2 diabetes.

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Section: Measurement Of Liver and Plasma Precursor Sterols By Gas Chrsupporting

confidence: 86%

Dual-action hypoglycemic and hypocholesterolemic agents that inhibit glycogen phosphorylase and lanosterol demethylase

Harwood

Petras

Hoover

et al. 2005

Journal of Lipid Research

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“…Indeed ergosterol, the major sterol of WT S. cerevisiae WA6 is synthetized. Moreover sterol biosynthesis continues alkylating unknown intermediates to 24-ethylidene sterols such as A7-avenasterol (X), a typical plant sterol [1] and 5~t-stigmasta-8,Z-24(241)-dien-313-ol (XI), found in Rubus fructicosus suspension cultures treated with AY 9744, an inhibitor of the AS-A7-sterol isomerase [23] (Fig. 2).…”

Section: Discussionmentioning

confidence: 99%

“…The stereochemistry of this transfer has been demonstrated [4]. In higher plants, the presence of 24-ethyl sterols results from two distinct methyl transfers from S-adenosyl-L-methionine [1,2]. According to the chemical structures of intermediates of sterol biosynthesis and substrate specificity studies, it is generally assumed that cycloartenol (V) is the substrate of the first methylation reaction resulting in 24-methylene cycloartanol (VI) [5,6], whereas 24-methylene lophenol (VII) is the preferred substrate for the second methylation resulting in 24-ethylidene lophenol (VIII) [7] (Fig.…”

Section: Introductionmentioning

confidence: 98%

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Transformation of Saccharomyces cerevisiae with a cDNA encoding a sterol C‐methyltransferase from Arabidopsis thaliana results in the synthesis of 24‐ethyl sterols

et al. 1996

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Using an EST-cDNA probe, a full-length cDNA (411) sequence of 1411 bp was isolated from A. thaliana. This sequence contained features typical of methyltransferases in general and in particular showed 38% identity with ERG6, a S. cerevisiae gene which encodes the zymosterol-C-24-methyltransferase. A yeast vector containing this ORF (4118-pYeDP60) was used to transform a wild type S. cerevisiae which accumulates predominantly ergosterol, a 24-methyl sterol as well as a mutant erg6 null mutant accumulating principally zymosterol, a sterol non-alkylated at C-24. In both cases, several 24-ethyl-and 24-ethylidene sterols were synthetized indicating that the 4118 cDNA encodes a plant sterol C-methyltransferase able to perform two sequential methylations of the sterol side chain.

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“…For separation by HPLC, samples were resuspended in chloroform-hexane (1:1) and were separated isocratically on a C18 Nucleosil column (250 mm by 5 jim) with a mobile phase of ethanol-methanolwater and were detected with a fixed-length UV detector set at 214 nm, with the data collected and analyzed as described above. By reversed-phase HPLC, sterols have characteristic retention times which are dependent on their structures (24,28). As one method of identifying these unknown lipids, a series of sterol standards was run under conditions identical to those under which the P. carinii samples were run, and the retention times were measured.…”

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confidence: 99%

Phytosterols are present in Pneumocystis carinii

Furlong

Samia

Rose

et al. 1994

Antimicrob Agents Chemother

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Although originally classified as a protozoan, Pneumocystis carinii is now considered to have fungal characteristics. Drugs typically used for the treatment of fungal infections target ergosterol. Because P. carinii is an important pathogen in AIDS and other immunocompromised patients, knowledge of the sterol content of this organism may be useful as a basis for developing new treatment strategies or for improving diagnosis. P. carinii organisms were harvested from infected rat lungs and were purified by filtration. Control preparations from uninfected animals were identically prepared. Lipids were extracted from the organisms and control preparations and were separated into neutral lipid, glycolipid, and phospholipid fractions by silicic acid chromatography. The neutral lipid fraction was further treated by alkaline hydrolysis and was analyzed by reversed-phase high-pressure liquid chromatography (HPLC), gas chromatography (GC), and GC-mass spectrometry (GC-MS). As shown by HPLC, the neutral lipid fraction from infected rats contained a minimum of six peaks, while in control preparations a single peak with a retention time identical to that of cholesterol was observed. The predominant sterol in these preparations was positively identified by GC-MS as cholesterol and constituted 80 to 90% of the total. The remaining peaks had relative retention times similar to those of phytosterols by both HPLC and GC, and the similarity of these sterols to those derived from plants and fungi was confirmed by MS. Ergosterol, however, was not present. These results provide further evidence for a close phylogenetic relationship between P. carinii and fungi and suggest that these sterols could be used as targets for drug development and for improving diagnosis.Pneumocystis carinii is one of the leading causes of opportunistic infection in AIDS patients (30). Despite the importance of this microorganism as an opportunistic pathogen, much basic information about the parasite is lacking. While originally classified phylogenetically as a protozoan, analyses of P. carinii DNA and mitochondrial and rRNA sequences have generally shown a higher degree of homology to the mitochondrial and rRNA sequences of fungi (yeasts) than to those of protozoa (9,13,27,31,34,35). The exact relationship remains to be determined. Analyses of 5S RNA have suggested a somewhat close phylogenetic relationship to members of the Rhizopoda-Myxomycota-Zygomycota group of "protista fungi." Other studies have suggested similarities to Saccharomyces, Candida, and Neurospora spp. and "red yeast" fungi. In general, the arguments in favor of classifying P. carinii as a protozoan are the amoeboid appearance of the trophic form, susceptibility to antiprotozoal drugs such as pentamidine isethionate or trimethoprim-sulfamethoxazole, insusceptibility to antifungal drugs such as amphotericin B, and the lack of ergosterol in Pneumocystis cell membranes. Arguments in favor of including P. carinii among the fungi include similarities of the sporogenous state to ascospore format...

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[1] A comparison of methods for the identification of sterols

Cited by 31 publications

References 83 publications

Dual-action hypoglycemic and hypocholesterolemic agents that inhibit glycogen phosphorylase and lanosterol demethylase

Dual-action hypoglycemic and hypocholesterolemic agents that inhibit glycogen phosphorylase and lanosterol demethylase

Transformation of Saccharomyces cerevisiae with a cDNA encoding a sterol C‐methyltransferase from Arabidopsis thaliana results in the synthesis of 24‐ethyl sterols

Phytosterols are present in Pneumocystis carinii

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