Lanosterol

About: Lanosterol is a research topic. Over the lifetime, 1239 publications have been published within this topic receiving 36737 citations. The topic is also known as: (3β)-lanosta-8,24-dien-3-ol & (3β,20R)-lanosta-8,24-dien-3-ol.

Effects of three azole derivatives on the lipids of different strains of Sporothrix schenckii.

Abstract: The comparative effects of ketoconazole, itraconazole, and fluconazole on the lipids of five Sporothrix schenckii strains were investigated. Quantitative analysis of lipids and sterols was completed, as well as qualitative analysis of sterols, by thin-layer chromatography and ultraviolet spectrophotometry. Growth of the S. schenckii isolates in the presence of azole derivative concentrations below the minimum inhibitory concentration (MIC) resulted in significant alterations in the lipid and sterol contents as compared with the control values. Furthermore, lanosterol was detected in these azole-treated cells. These results were in complete agreement with the proposed mechanism of action of azoles, which act by inhibiting ergosterol biosynthesis with a consequent accumulation of lanosterol. Concerning the MIC values, fluconazole was found to be the least effective drug. On the other hand, as determined from a comparison of the effects of the three azoles on the sterol content of the strains studied, no significant differences in efficacy were found among the tested drugs.

Biosynthesis of sterols by a yeast homogenate. Incorporation of mevalonic acid into cholesta-5,7,24-trien-3beta-ol and 5alpha-cholesta-7,24-dien-3beta-ol.

Abstract: Incubation of (3RS, 2R)-[2-14C, 2-3H]mevalonic acid and (3RS, 2S)-[2-14C, 2-3H]mevalonic acid with mechanically disrupted yeast cells resulted in C27-metabolites Two (14C5, 3H4)-metabolites, cholesta-5,7,24-trien-3β-ol and 5α-cholesta-7,24-dien-3β-ol, were isolated and characterized The impairment of the 24-methyl transferase system was confirmed by the lack of incorporation of 14C into the sterol fraction on incubation of S-adenosyl-l-[methyl-14C]methionine with the yeast homogenate The results indicate that interference with the (C-24)-alkylating system did not prevent the transformation of lanosterol to the cholesta-5,7,24-trien-3β-ol and to 5α-cholesta-7,24-dien-3β-ol It can therefore be inferred that transformations of the nucleus and of the side chain can function independently However our results do not provide a definition of the actual sequence of the metabolic events between lanosterol and ergosterol

Lanosterol 14 alpha-demethylase (cytochrome P-45014DM): modulation of its enzyme activity by cholesterol feeding.

Abstract: Regulation of the activity of lanosterol 14α-demethylase (cytochrome P-45014DM) by dietary cholesterol was studied in rats. In male rats fed a 3% cholesterol diet for 1 and 4 weeks, the activity of 24, 25-dihydrolanosterol 14α-demethylase was decreased in the liver. The cytochrome P-45014DM protein content detected by immunoblotting was also decreased by cholesterol feeding. These results demonstrate that dietary cholesterol acts as a repressive factor for lanosterol 14α-demethylase. Further, the activity was enhanced by preincubation with phosphatase of the enzyme solution from both the control and cholesterol fed rats at the same rate. This result suggests that regulation of the activity involves phosphorylation of this enzyme.

The construction and characterization of self-sufficient lanosterol 14-demethylase fusion proteins consisting of yeast CYP51 and its reductase.

Abstract: Two forms of a self-sufficient lanosterol 14-demethylase fused enzyme consisting of Saccharomyces cerevisiae CYP51 and S. cerevisiae reduced nicotinamide-adenine dinucleotide phospahte (NADPH)-P450 reductase were constructed and characterized. The two forms of fused enzymes, F1 and F2, which had slight differences in the linker regions between their P450 and reductase domains, were expressed in Escherichia coli cells. Both F1 and F2 were purified to homogeneity. The purified preparations of F1 and F2 showed spectral properties of not only P450 but also flavoprotein. F1 and F2 showed lanosterol 14-demethylase activity with kinetic parameters comparable to those obtained with a reconstituted system consisting of S. cerevisiae CYP51 and S. cerevisiae NADPH-P450 reductase. These facts indicate that F1 and F2 are self-sufficient lanosterol 14-demethylases that can catalyze three successive monooxygenations with comparable activity to naturally occurring CYP51. The enzymatic reduction of the CYP51 in F1 and F2 was faster than that of the CYP51 in the reconstituted system. The results of dilution experiments suggested that the electron transfer from the reductase domain to the CYP51 domain in F1 and F2 occurred both intra- and intermolecularly. Two fused self-sufficient lanosterol 14-demethylases were successfully constructed. This is the first example of the purified preparation of an artificial self-sufficient P450 monooxygenase that catalyzes the oxidative cleavage of C-C bond via three successive monooxygenations.