Disease relevance of lanosterol

• Thus, the contents of the two lathosterols and the two methostenols were clearly higher in the gallstones, whereas lanosterol stayed almost totally, and other minor sterols were preferentially, in the bile [1].
• Thus, for elimination of both of the 4-methyl groups of lanosterol, the 10 individual reactions catalyzed in this multicomponent system are identical in liver and hepatoma 7777 microsomes, and the rate-determining stop for both liver and hepatoma is the inital oxidative attack on the 4alpha-methyl group of cholesterol procursors [2].
• Expression of the M. capsulatus MCCYP51FX fusion in Escherichia coli yielded a P450, which, when purified to homogeneity, had the predicted molecular mass approximately 62 kDa on SDS/PAGE and bound lanosterol as a putative substrate [3].
• Sterols in membranes: growth characteristics and membrane properties of Mycoplasma capricolum cultured on cholesterol and lanosterol [4].
• Mechanisms of resistance to azoles in Candida albicans, the main etiologic agent of oropharyngeal candidiasis (OPC), include alterations in the target enzyme (lanosterol demethylase) and increased efflux of drug [5].

Psychiatry related information on lanosterol

• Serum concentrations of different sterols related to cholesterol were measured.Serum levels of lathosterol and lanosterol correlated negatively with cognitive performance on the Word Learning tests for verbal learning and memory [6].

High impact information on lanosterol

• Supernatant protein factor, which stimulates the conversion of squalene to lanosterol, is a cytosolic squalene transfer protein and enhances cholesterol biosynthesis [7].
• Surprisingly, when erg27 was grown on cholesterol- or ergosterol-supplemented media, the endogenous compounds that accumulated were noncyclic sterol intermediates (squalene, squalene epoxide, and squalene dioxide), and there was little or no accumulation of lanosterol or 3-ketosterols [8].
• The definitive structural identities of two C-24 alkylated lanosterol compounds, previously not reported for rat-derived P. carinii carinii, were determined by using GLC, MS, and NMR spectroscopy together with the chemical syntheses of authentic standards [9].
• One suppressor mutation is erg11, which is blocked in 14alpha-demethylation of lanosterol and is itself an auxotroph [10].
• Suppression of erg25 by erg11 slu1 (or erg11 slu2) results in a slow-growing strain in which lanosterol, the first sterol in the pathway, accumulates [10].

Chemical compound and disease context of lanosterol

• 24(R,S),25-Iminolanosterol (IL) and triparanol added to cultures of rat hepatoma cells, H4-II-C3 (H4), interrupt the conversion of lanosterol to cholesterol and, depending on their concentrations, cause the accumulation in the cells of intermediates in the lanosterol to cholesterol conversion [11].
• Similarly lanosterol and its partially demethylated derivatives satisfy the sterol requirement of Mycoplasma capricolum [12].

Biological context of lanosterol

• We report the cloning, characterization, and overexpression of Saccharomyces cerevisiae ERG7, which encodes lanosterol synthase [(S)-2,3-epoxysqualene mutase (cyclizing, lanosterol forming), EC 5.4.99.7], the enzyme responsible for the complex cyclization/rearrangement step in sterol biosynthesis [13].
• A cDNA encoding rat oxidosqualene lanosterol-cyclase [lanosterol synthase; (S)-2,3-epoxysqualene mutase (cyclizing, lanosterol-forming), EC 5.4.99.7] was cloned and sequenced by a combination of PCR amplification, using primers based on internal amino acid sequence of the purified enzyme, and cDNA library screening by oligonucleotide hybridization [14].
• Finally, we identified lanosterol as a candidate endogenous ligand that induces coactivator recruitment and transcriptional activation by mFXRbeta [15].
• The active site cavity must therefore be at least 10 A high directly above the iron atom and pyrrole ring C of the heme group, and lanosterol binds to the enzyme in the region above pyrrole ring C [16].
• Cytochrome P-450-dependent oxidation of lanosterol in cholesterol biosynthesis. Microsomal electron transport and C-32 demethylation [17].

Anatomical context of lanosterol

• Differential effects of cholesterol and lanosterol on artificial membranes [18].
• Microsomal enzymes of cholesterol biosynthesis from lanosterol. Purification and characterization of delta 7-sterol 5-desaturase of rat liver microsomes [19].
• Biphasic modulation of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMG-CoA reductase) has been demonstrated in primary hepatocyte cultures treated with the lanosterol 14 alpha-methyl demethylase inhibitor miconazole [20].
• When cultured cells are treated with the fluorinated lanosterol analogue, a decrease in 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase activity and immunoreactive protein was observed [21].
• However, when the lanosterol 14 alpha-methyl demethylase-deficient mutant cell line, AR45, is treated with the fluorosterol, no effect upon HMG-CoA reductase is observed [21].

Associations of lanosterol with other chemical compounds

• Because the membrane behavior of 4,4-dimethylcholesterol is closely similar to that of cholesterol, it is concluded that the axial 14-alpha-methyl group is responsible for the lessened membrane immobilization of lanosterol [18].
• Whereas vertebrates and fungi synthesize sterols from epoxysqualene through the intermediate lanosterol, plants cyclize epoxysqualene to cycloartenol as the initial sterol [22].
• By contrast, several resonances attributable to quaternary carbon atoms or methyl groups are seen in the 13C nuclear magnetic resonance spectrum of lanosterol/lecithin vesicles, indicating that lanosterol is much less immobilized than cholesterol [18].
• A yeast mutant lacking lanosterol synthase [(S)-2,3-epoxysqualene mutase (cyclizing, lanosterol forming), EC 5.4.99.7] was transformed with an A. thaliana cDNA yeast expression library, and colonies were assayed for epoxysqualene mutase activity by thin-layer chromatography [22].
• Upon aerobic incubation of microsomes from semianaerobically grown yeast cells in the presence of NADPH and cyanide, endogenous lanosterol was converted to 4,4-dimethylzymosterol [23].

Gene context of lanosterol

• Many facets of mammalian lanosterol 14alpha-demethylase from the evolutionarily conserved cytochrome P450 family CYP51 [24].
• Lanosterol metabolism and sterol regulatory element binding protein (SREBP) expression in male germ cell maturation [25].
• In these cells, both lanosterol analogs lowered HMGR protein levels without affecting LDLR concentration [26].
• ARE2 overexpression had no impact on the accumulation of the early sterols such as lanosterol, but influenced the later intermediates and the end product ergosterol [27].
• The oxidosqualene cyclase (Erg7p) encoded by the ERG7 gene converts oxidosqualene to lanosterol, the first cyclic component of sterol biosynthesis [28].

Analytical, diagnostic and therapeutic context of lanosterol

• In both free and trimethylsilylated forms, this metabolite showed a relative retention time (relative to lanosterol) of 1.10 in gas chromatography on OV-17 columns [23].
• Cholesterol biosynthesis from lanosterol. Molecular cloning, tissue distribution, expression, chromosomal localization, and regulation of rat 7-dehydrocholesterol reductase, a Smith-Lemli-Opitz syndrome-related protein [29].
• Results using a radio-high performance liquid chromatography (HPLC) assay show that in rat liver microsomal preparations, with [24,25-3H]dihydrolanosterol as substrate, the compounds do indeed inhibit the biosynthesis of sterols downstream from lanosterol [30].
• A Northern blot technique was used to monitor expression of ERG11 (encoding lanosterol demethylase) and genes coding for efflux pumps [5].
• The effect of cholesterol and lanosterol on the formation of structures in the gel/subgel phase of 1,2-dipalmitoylphosphatidylcholine was investigated using freeze-fracture electron microscopy and X-ray diffraction [31].

References