Showing papers on "Sterol published in 1985"
TL;DR: It is concluded that the membrane-bound domain of reductase plays a crucial role in the rapid and regulated degradation of this ER protein.
374 citations
TL;DR: The critical domain role for sterol is observed under conditions of lanosterol supplementation where low levels of ergosterol (10-times those necessary for sparking on cholestanol) are required for growth.
243 citations
TL;DR: Results indicate that cholesterol, plant sterols, and 5 alpha-stanols are deposited prematurely and are associated with accelerated atherosclerosis in subjects with sitosterolemia with xanthomatosis.
217 citations
TL;DR: It is suggested that modulation of sperm lipid levels comprises an event of capacitation and that albumin mediates this process through its activity as a sterol acceptor.
Abstract: The role of albumin in mouse sperm capacitation was studied in relation to its activities as a lipid-solubilizing protein and a sterol acceptor. Two bovine serum albumins (BSA) which supported capacitation, Fraction V and fatty acid-free, both contained cholesterol and phospholipid but were without detectable levels of serum high-density lipoprotein (HDL). The lipid content of BSA could be reduced by trichloroacetic acid (TCA) precipitation; however, removal of all detectable lipids required precipitation with ethanolic acetone and diethyl ether extraction. In medium supplemented with Fraction V, fatty acid-free, or TCA-precipitated BSA, mouse sperm were capacitated as evidenced by their ability to fertilize eggs, concomitant with decreases in total cellular sterol and increases in phospholipid content. Delipidated BSA, fractionated on Sephadex G-100 in guanidine HCl also supported capacitation and mediated a 20% decrease in sperm sterol content, while cellular phospholipid levels remained unchanged. When BSA was modified by cholesterol augmentation, fertilization was inhibited in a cholesterol dose-dependent manner. These findings suggest that modulation of sperm lipid levels comprises an event of capacitation and that albumin mediates this process through its activity as a sterol acceptor.
208 citations
TL;DR: Conservation of the structure of the membrane-bound domain in HMG-CoA reductase supports the hypothesis that sterol-regulated degradation is an important mechanism for suppression of reduct enzyme activity and for regulation of cholesterol metabolism in humans as well as in hamsters.
180 citations
TL;DR: Seven species of fresh mangrove leaves were homogenized using chloroform—methanol and the extract was diluted with water to precipitate out triterpenoids and sterols, which were separated into neutral and acidic fractions.
136 citations
TL;DR: Assessment of plasma sterol composition in subjects with sitosterolemia and xanthomatosis indicates that abnormally high plasma concentrations of cholestanol, 5 alpha-campestanol- and 5alpha-sitostanol are found, and that treatment with cholestyramine effectively reduced elevated Plasma sterol levels.
122 citations
TL;DR: The present investigation was conducted to compare homogeneous preparations of FABP and SCP-2 with respect to their capacities to participate as carrier proteins in reactions involving sterols or fatty acids, and shows that they have separate and distinct physiological functions.
110 citations
TL;DR: In this paper, a method was developed for the rapid, accurate analysis of C-7 oxdized cholesterol derivatives (C-7 OCDs) in muscle and other foods.
Abstract: A method was developed for the rapid, accurate analysis of C-7 oxdized cholesterol derivatives (C-7 OCDs) in muscle and other foods. The method avoids saponification. Total lipid extracts were fractionated on silica gel columns to concentrate trace sterol oxides from triglycerides, cholesterol, and phospholipids. Sterol oxides in eluates were quantified by normal-phase high performance liquid chromatography. Recoveries of C-7 OCDs added to beef approached 100%. Pancake mix, French fries, and organ product “concentrates” sold in health food stores contained from 1 to 70 ppm of C-7 OCDs (7-keto, 7α-hydroxy and 7β-hydroxycholesterol), but none could be detected in raw beef, fried chicken, cooked hamburger, beef jerky or liver sausage.
109 citations
TL;DR: The results described in the present review support the concept that intracellular lipid transfer is a highly specific process, far more substrate-specific than suggested by the earlier studies conducted using liposomal techniques.
107 citations
TL;DR: Biosynthetically tritiated sterols from Chinese hamster lung (Dede) cells were fractionated by high performance liquid chromatography, and fractions were assayed for their ability to repress 3-hydroxy-3-methylglutaryl-CoA reductase in L cell cultures.
TL;DR: After derivatization as trimethylsilyl ethers the foregoing diols, alpha-epoxide, cholestane-triol, 7-ketocholesterol, and cholesta-3,5-dien-7-one were completely resolved on a DB-1 column.
TL;DR: By utilizing mutants, the simple eukaryotic system of yeast may be extended to explore the entire field of sterol metabolism and its relationship to cellular physiology.
Abstract: Yeast mutants defective in ergosterol synthesis are valuable tools for investigating sterol metabolism. Both sterol mutants and sterol auxotrophs have been utilized in determining what sterol structural features are required for yeast cell viability. Both types of mutants can also be studied to ascertain how changes in sterol structure affect membrane properties. Other aspects of sterol metabolism, such as the specificity of sterol esterification, have been elucidated by the sterol auxotrophs. In broader applications, interrelationships between sterol metabolism and other cellular functions (e.g., heme metabolism) may also be examined with these mutants. By analyzing the lipid composition of the sterol mutants, on the other hand, much of the ergosterol biosynthetic pathway has been delineated. The unusual sterols of the mutants can also be obtained to develop assays for the enzymes involved in ergosterol synthesis. Thus, by utilizing mutants, the simple eukaryotic system of yeast may be extended to explore the entire field of sterol metabolism and its relationship to cellular physiology.
TL;DR: The results suggest that cholesterol may be concentrated for delivery to the plasma membrane by being synthesized from a sterol precursor such as lanosterol in a discrete but undefined intracellular membrane.
TL;DR: It appears most likely that the hypocholesterolaemic effects of this cereal fibre preparation can be explained by increased faecal steroid excretion and not through inhibition of cholesterogenesis by volatile fatty acids of large bowel origin.
TL;DR: The chromatographic and spectrometric sterol analyses and the isotopic tracer findings suggested that ketoconazole impaired the cytochrome P-450 dependent 14 alpha-demethylation of lanosterol, that cholesterol was neither biosynthesized nor metabolized, and that the physiological functions of 5-dehydroepisterol had sterol structural requirements not entirely met by cholesterol.
TL;DR: Compared to other cultures, Tarahumara Indians had a reduced ability to absorb dietary cholesterol and higher total sterol turnover primarily because of an increased bile acid output.
TL;DR: In this paper, the capability of sponges to convert Δ 5 - into Δ 5,7 -sterols, which was as efficient as the conversion of Δ 7 -to Δ 5,7 -structure common to plant and yeast sterols, was demonstrated by double labelling experiments.
TL;DR: Growth and sterol synthesis of Aspergillus fumigatus and A. niger were studied in control cultures and in the presence of ketoconazole or itraconazole, the latter compound being 100 times more growth inhibitory than the former.
Abstract: Growth and sterol synthesis of Aspergillus fumigatus and A. niger were studied in control cultures and in the presence of ketoconazole or itraconazole, the latter compound being 100 times more growth inhibitory than the former. Sterol synthesis is inhibited more rapidly than any visible fungal outgrowth. This inhibition results in an accumulation of 4,14 dimethyl- and 4,4',14 trimethylsterols. The presence of these membrane-disturbing sterols may result in a pertubation of membrane-bound enzyme systems such as chitin synthase.
TL;DR: A procedure was developed which allowed selection of strains which would take up exogenous sterols but had no apparent defect in heme or ergosterol biosynthesis, and one of these sterol uptake control mutants possessed an allele which allowed phenotypic expression of sterol auxotrophy in a heme-competent background.
Abstract: Wild-type Saccharomyces cerevisiae do not accumulate exogenous sterols under aerobic conditions, and a mutant allele conferring sterol auxotrophy (erg7) could be isolated only in strains with a heme deficiency. delta-Aminolevulinic acid (ALA) fed to a hem1 (ALA synthetase-) erg7 (2,3-oxidosqualene cyclase-) sterol-auxotrophic strain of S. cerevisiae inhibited sterol uptake, and growth was negatively affected when intracellular sterol was depleted. The inhibition of sterol uptake (and growth of sterol auxotrophs) by ALA was dependent on the ability to synthesize heme from ALA. A procedure was developed which allowed selection of strains which would take up exogenous sterols but had no apparent defect in heme or ergosterol biosynthesis. One of these sterol uptake control mutants possessed an allele which allowed phenotypic expression of sterol auxotrophy in a heme-competent background.
TL;DR: Results show that SCP2 enhances 7 alpha-hydroxycholesterol formation by rat liver microsomes (microsomal fractions), utilizing either endogenous membrane cholesterol, cholesterol supplied exogenously in serum or in the form of cholesterol/phospholipid liposomes.
Abstract: Sterol carrier protein2 (SCP2) is known to stimulate utilization of cholesterol in enzymic reactions in which cholesterol is the substrate. Substantial recent experimental evidence indicates that SCP2: activates enzymic conversion of intermediates between lanosterol and cholesterol; stimulates the microsomal conversion of cholesterol into cholesterol ester in rat liver; and enhances mitochondrial utilization of cholesterol for pregnenolone formation in the adrenals. The conversion of cholesterol into 7 alpha-hydroxycholesterol is the rate-limiting step in bile-acid synthesis. We therefore investigated the effect of SCP2 on this physiologically critical reaction by using a gas-chromatography-mass-spectrometry procedure that measures the mass of 7 alpha-hydroxycholesterol formed. The results show that SCP2 enhances 7 alpha-hydroxycholesterol formation by rat liver microsomes (microsomal fractions), utilizing either endogenous membrane cholesterol, cholesterol supplied exogenously in serum or in the form of cholesterol/phospholipid liposomes. Microsomes immunotitrated with anti-SCP2 antibody exhibited considerably less capacity to synthesize 7 alpha-hydroxycholesterol, which was restored to control levels on addition of purified SCP2. These data are consistent with the suggestion that SCP2 may be of physiological significance in the overall metabolism of cholesterol.
TL;DR: It is demonstrated that cholesterol sulfate suppresses de novo sterol synthesis in cultured human fibroblasts and is a potent inhibitor of the enzyme, 3-hydroxy-3-methylglutaryl coenzyme A reductase (mevalonate): NADP+ oxidoreductase (CoA-acylating), the rate-limiting enzyme in cholesterol biosynthesis.
TL;DR: The effect of ergosterol on cell division and phospholipid metabolism was investigated in Saccharomyces cerevisiae strain GL7, a sterol and unsaturated fatty acid auxotroph and the growth rate increased.
TL;DR: This analogue of a high energy intermediate was found to be a very potent and specific inhibitor of the two enzymatic reactions both in vitro and in vivo.
TL;DR: The results show that at least some of the biochemical processes of Acanthamoeba polyphaga might be phylogenetically related to those of unicellular algae.
Abstract: The soil amoeba Acanthamoeba polyphaga is capable of synthesizing its sterols de novo from acetate. The major sterols are ergosterol and poriferasta-5,7,22-trienol. Furthermore C28 and C29 sterols of still unknown structure with an aromatic B-ring are also synthesized by the amoeba. The first cyclic sterol precursor is cycloartenol, which is the sterol precursor in all photosynthetic phyla. No trace of lanosterol, which is the sterol precursor in animals and fungi, could be detected. These results show that at least some of the biochemical processes of Acanthamoeba polyphaga might be phylogenetically related to those of unicellular algae. Addition of exogenous sterols to the culture medium does not influence the sterol biosynthesis and the sterol composition of the cells.
TL;DR: Measurement of stoichiometry of 5-desaturase demonstrates that for each equivalent of cis-desaturation of delta 7-cholestenol, 1 eq of NADH is consumed, which confirms, as suggested by previous workers, that the 5- Desaturase is catalyzed by a mixed function oxidase rather than a dehydrogenase.
TL;DR: Sterol side-chain (C-24) methylation was assayed by incorporation of radioactivity from [Me-14C]methionine into the ergosterol fraction in cells of the pathogenic fungi Candida albicans, Candida parapsilosis and Trichophyton mentagrophytes to measure ergosterols biosynthesis inhibition by the allylamine antimycotics naftifine and SF 86-327.
Abstract: Summary: Sterol side-chain (C-24) methylation was assayed by incorporation of radioactivity from [Me-14C]methionine into the ergosterol fraction in cells of the pathogenic fungi Candida albicans, Candida parapsilosis and Trichophyton mentagrophytes. Methylation at C-24 occurred after nuclear demethylation in all cases. The method was used to measure ergosterol biosynthesis inhibition by the allylamine antimycotics naftifine and SF 86-327, which are known to block squalene epoxidation. In C. albicans cells treated with SF 86-327 (1 mg 1-1) to fully inhibit squalene epoxidation, C-24 methylation continued for several hours at about 40% of the control rate. This residual biosynthesis was probably due to methylation of endogenous sterol precursors. The degree of residual biosynthesis in the three fungi correlated well with their susceptibility to SF 86-327. The highly susceptible dermatophyte T. mentagrophytes had negligible residual sterol biosynthesis. These differences were not due to inhibition of methionine uptake. For naftifine (100 mg 1-1) there was evidence of a second inhibitory action C. albicans. A cell-free assay indicated that this was due to direct inhibition of the C-24 methyltransferase.
TL;DR: Cholesterol synthesis and its diurnal variation was studied by measuring squalene, free and esterified methyl sterols and cholesterol, and triglycerides in serum lipoproteins every four hours over a period of 24 hours in controls and in patients with jejunoileal bypass or ileal exclusion.
Abstract: Cholesterol synthesis and its diurnal variation was studied by measuring squalene, free and esterified methyl sterols and cholesterol, and triglycerides in serum lipoproteins every four hours over a period of 24 hours in controls and in patients with jejunoileal bypass or ileal exclusion. Fat absorption, as indicated by postprandial increase of very-low-density lipoprotein (VLDL) lipids (including chylomicrons) and fecal fat, was markedly impaired in jejunoileal bypass. Fecal analysis indicated that bile acid malabsorption enhanced cholesterol synthesis about sixfold in ileal dysfunction, and twofold in jejunoileal bypass with moderate bile acid and cholesterol malabsorption. The squalene contents were not increased consistently in the VLDL and combined low-density plus high-density lipoproteins (LDL + HDL) of the two operated groups and, in contrast to the controls, the diurnal variation was inconsistent. The levels of unesterified methyl sterols, Δ 8 -dimethylsterol and Δ 8 -methostenol in particular, were several times higher throughout the 24 hour period in the lipoproteins of the two patient groups than of the controls, were higher in ileal dysfunction than jejunoileal bypass, exhibited a constant diurnal rhythm in the controls but only in the relatively small VLDL fraction (not in the large LDL + HDL) of the operated groups, and were positively correlated with cholesterol synthesis in the three groups combined (for methyl sterols in VLDL r = 0.740 and in LDL + HDL r = 0.869). Esterified methyl sterols were also increased in the operated groups but were not correlated with cholesterol synthesis. The findings suggest that circadian rhythm regulates cholesterol synthesis, even at a high rate of production, that long-lasting stimulation of cholesterol synthesis modifies conversion of squalene to cholesterol, and that the response of the methyl sterol contents of serum lipoproteins to enhanced fecal elimination of cholesterol is mainly determined by the magnitude of increased cholesterol synthesis most likely in the liver.
TL;DR: The dependence of the rates of sterol-polyene antibiotic interaction on the phospholipid composition of the vesicles indicates that phospholipsicles may be an inadequate model for reaching a comprehensive understanding of the effects exerted on biological membranes by these agents.