Showing papers on "Sterol published in 1977"

A comparison of hypocholesterolemic activity of β-sitosterol and β-sitostanol in rats

Abstract: The hypocholesterolemic activity of beta-sitosterol and its hydrogenated product, beta-sitostanol (dihydrositosterol or stigmastanol) has been compared in young male rats. When cholesterol was included in the diet, sitostanol consistently exhibited significantly greater hypocholesterolemic activity than sitosterol. There were no apparent differences in the effects of the sterol and the stanol on the concentration of liver cholesterol and triglyceride. Increases in plasma triglyceride due to feeding sitosterol were not observed with sitostanol. Incorporation of dietary sitostanol into plasma, liver and other tissues was always negligible, and thus this stanol was almost completely recovered in feces, while there was considerable deposition of sitosterol (mean fecal recovery being 85% to 92%). The increase in fecal output of dietary cholesterol was significantly greater with the stanol than with sterol. There was no demonstrable negative effect on growth and weight of major visceral tissues in rats fed the sterol as well as the stanol. These observations together with those reported previously indicate that hydorgenation of phytosterols is a novel approach to enhance their hypocholesterolemic activities without influencing the relative safety of the initial sterols.

Regulation of cholesterol synthesis by low density lipoprotein in isolated human lymphocytes

Abstract: The rate of cholesterol synthesis from [14C]acetate was low in circulating blood lymphocytes freshly isolated from 17 normal subjects and 4 subjects with homozygous FH. On the other hand, the rate of cholesterol synthesis was two to fourfold above normal in freshly isolated lymphocytes from two subjects with abetalipoproteinemia. When the lymphocytes from subjects with all three genotypes were incubated for 48-72 h in the absence of lipoproteins, the rate of cholesterol synthesis increased by 5-15-fold. The subsequent addition of plasma LDL, but not HDL, rapidly suppressed cholesterol synthesis in the lymphocytes from normal subjects. In contrast, lymphocytes from the FH homozygotes, which have been shown previously to be deficient in cell surface LDL receptors, were resistant to LDL-mediated suppression of cholesterol synthesis. In addition to its ability to suppress cholesterol synthesis after it had been elevated by incubation of the cells in the absence of lipoproteins, LDL was able to suppress the induction of the enhanced rate of sterol synthesis when added to normal lymphocytes immediately after their isolation from the bloodstream. In contrast to the former action of LDL, the latter action of LDL-i.e., the suppression of induction of sterol synthesis-also occurred to a limited extent in lymphocytes from FH homozygotes. However, the FH lymphocytes, but not the normal cells, could be made resistant to this action of LDL by inclusion in the incubation medium of lipoprotein-deficient serum (30 percent, vol/vol) plus HDL (1 mg protein/ml). Considered together with previous data demonstrating a deficiency of LDL receptors in freshly isolated lymphocytes from FH homozygotes, the current studies provide evidence in support of the hypothesis that the interaction of plasma LDL with its cell surface receptor serves to regulate cholesterol synthesis in human lymphocytes.

Differential effects of cholesterol and lanosterol on artificial membranes

Abstract: The effects of cholesterol, 4,4-dimethylcholesterol, and lanosterol (4,4',14alpha-trimethyl-delta8,24-cholestadiene-3beta-ol) on some properties of lecithin vesicles have been compared. Unlike cholesterol, lanosterol retards the exit of trapped glucose from phospholipid vesicles only slightly. The 13C nuclear magnetic resonance spectrum of cholesterol/lecithin vesicles shows no resonances attributable to the sterol. 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. 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. The results emphasize the importance of a planar sterol alpha-face for interaction with phospholipid acyl chains.

Microbial cleavage of sterol side chains.

Abstract: Publisher Summary This chapter discusses the microbial cleavage of sterol side chains. The recent interest in the microbial conversion of sterols to C19 steroids was caused by the increased demand for steroid drugs and the shortage of diosgenin. As the microbial process has to compete with chemical methods, high conversion efficiencies in the presence of large substrate concentrations have to be obtained. These processes are now used on an industrial scale for the production of 17-ketosteroids. Conventional chemical oxidation of the saturated aliphatic chain results in very low yields. However, in using remote oxidation, the removal of the cholesterol side chain proceeds rather efficiently. For the chemical oxidation of unsaturated sterol side chains, there exist few methods. As alternative to chemical methods, the microbial removal of the aliphatic side chain of phytosterols offers a promising method for use of these sterols and has been studied for some time. Recently, processes for the commercial conversion of sterols to C19-steroids by microorganisms have been developed.

Differential effects of cholesterol and lanosterol on artificial membranes (glucose permeability/ 13 C nuclear magnetic resonance spectroscopy)

Abstract: The effects of cholesterol, 4,4-dimethylcholesterol, and lanosterol (4,4',14α-trimethyl-δ 8,24 -cholestadiene-3β-ol) on some properties of lecithin vesicles have been compared. Unlike cholesterol, lanosterol retards the exit of trapped glucose from phospholipid vesicles only slightly. The 13 C nuclear magnetic resonance spectrum of cholesterol/lecithin vesicles shows no resonances attributable to the sterol. By contrast, several resonances attributable to quaternary carbon atoms or methyl groups are seen in the 13 C nuclear magnetic resonance spectrum of lanosterol/lecithin vesicles, indicating that lanosterol is much less immobilized than cholesterol. Because the membrane behavior of 4,4-dimethylcholesterol is closely similar to that of cholesterol, it is concluded that the axial 14-α-methyl group is responsible for the lessened membrane immobilization of lanosterol. The results emphasize the importance of a planar sterol α-face for interaction with phospholipid acyl chains.

The Interaction of Dietary Fibers and Cholesterol upon the Plasma Lipids and Lipoproteins, Sterol Balance, and Bowel Function in Human Subjects

Abstract: To identify any metabolic effects of dietary fiber upon cholesterol metabolism in man, six adult volunteer subjects were fed eucaloric cholesterol-free formula diets, with and without added dietary fiber for two 4-wk periods. A large quantity of dietary fiber was fed, some 60 g of plant cell wall material (or 16 g of crude fiber) derived from corn, beans, bran, pectin, and purified cellulose. This provided about five times the fiber intake of the typical American diet. The addition of fiber to the cholesterol-free diet did not change either the plasma cholesterol level (171+/-21 mg/dl, SEM, to 167+/-18) or the triglyceride (103+/-39 to 93+/-27 mg/dl). The excretion of both endogenous neutral steroids and bile acids were unchanged with fiber (505+/-41 to 636+/-75 mg/day and 194+/-23 to 266+/-47 mg/day, respectively.) However, total fecal steroid excretion was increased 699+/-29 to 902+/-64 mg/day, P < 0.025). With fiber, intestinal transit time was decreased (59+/-9 to 35+/-8 h, P < 0.005), and both the wet and dry stool weights were greatly increased.A second group of six subjects was fed similar diets containing 1,000 mg cholesterol derived from egg yolk. The addition of fiber to the 1,000-mg cholesterol diet did not alter either plasma cholesterol level (233+/-26 to 223+/-36 mg/dl) or triglyceride (102+/-19 to 83+/-11 mg/dl). The excretion of endogenous neutral steroids (618+/-84 to 571+/-59 mg/day), of bile acids (423+/-122 to 401+/-89 mg/day), and of total fecal steroids (1,041+/-175 to 972+/-111 mg/day) were unchanged by fiber. The absorption of dietary cholesterol was not altered when fiber was added to the 1,000-mg cholesterol diet (44.0+/-3.3 to 42.9+/-2.5%). A two-way analysis of variance utilizing both groups of subjects indicated a significant (P < 0.001) effect of dietary cholesterol upon the plasma cholesterol concentration. We concluded that a large quantity of dietary fiber from diverse sources had little or no effect upon the plasma lipids and sterol balance in man in spite of the fact that intestinal transit time and stool bulk changed greatly.

Antagonistic Action of Lipid Components of Membranes from Candida albicans and Various Other Lipids on Two Imidazole Antimycotics, Clotrimazole and Miconazole

Abstract: The growth-inhibitory activity of two imidazole antimycotics, clotrimazole and miconazole, against Candida albicans was significantly reversed when lipid extracts from protoplast membranes of the same organism were added to the assay medium together with the drugs. Of four major classes of lipids further separated from them, viz., phospholipids, triglycerides, sterol esters, and free sterols, the former two were capable of counteracting both drugs, whereas the latter two were not. However, even with phospholipids or triglycerides, no antagonism was noted when they were saturated by catalytic hydrogenation before use. The antagonistic effect of varying classes of commercial lipids, including phospholipids, acylglycerides, sterols, and fatty acids, was also studied by means of the agar diffusion technique. Significant antagonism to both drugs was observed with: (i) phospholipids with an unsaturated acyl group; (ii) acylglycerides, the ester portion of which consists of unsaturated fatty acid; (iii) ultraviolet-activated sterols; and (iv) unsaturated fatty acids of cis -configuration. By contrast, none of the saturated phospholipids and acylglycerides nor sterols was effective as an antagonist. With the exception only of lauric acid, all of a series of saturated fatty acids and unsaturated trans -fatty acids ranging from C 8 to C 18 in chain length were either minimally effective or completely ineffective. Essentially, there was no qualitative difference between clotrimazole and miconazole in the response to these various lipids.

Sterols in fungi: their functions in growth and reproduction.

Abstract: Publisher Summary This chapter focuses on the Phytophthoru cuctorum, which grows on a simple medium containing sucrose, asparagines, mineral salts and thiamin, but on this medium it remains purely vegetative On the other hand, when grown on oatmeal agar, oospores are produced in abundance The factors in oats responsible for the difference have been found to be sterols Addition of sterols to the simple basal medium changed the mode of growth from vegetative to reproductive The role that sterols play in controlling reproduction in ascomycetes is not yet clear The importance of sterols as essential structural components of membranes and their consequent importance in efficient metabolism are well established in yeast, but their precise functions are still hardly understood In the zygomycetes, control of reproduction by trisporic acid is well understood It is surprising that more fungi cannot synthesize sterols, as they mostly inhabit environments where sterols would be expected to occur The sterol content of spores of Plusmodiophoru brassicue varies significantly according to the sterol composition of the host, suggesting at least partial heterotrophy

Sterol mutants ofSaccharomyces cerevisiae: Chromatographic analyses

Abstract: The sterols accumulated by ergosterol deficient mutants of the genes erg6, erg2, erg3, and erg5 (formerly po11, po12, po13, and po15) have been analyzed by gas liquid chromatography. Together with pure sterols obtained from the mutants, they were characterized on SE-30, OV-17, and OV-225. The effects of molecular structure on the retention characteristics of a range of C28 ergostane sterols have been studied. The double mutants obtained by crossing the single mutants were also analyzed and their sterols identified where possible. The effects of the erg mutations on the control of sterol biosynthesis in yeast are discussed.

Isolation and partial characterization of a cholesterol-requiring mutant of Chinese hamster ovary cells

Abstract: A sterol-requiring mutant has been isolated from mutagenized Chinese hamster ovary cells. This mutant grows normally only when cholesterol is present in the medium. Cell lysis occurs within 3 days in the absence of cholesterol. The frequency of reversion of this mutant to prototrophic growth is low (less than or equal to 10(-6). Whole cell pulse experiments with [14C]acetate or [3H]mevalonate indicate that the rate of synthesis of digitonin-precipitable material is greatly diminished in the mutant cells as compared to that in normal Chinese hamster ovary cells. Enzyme assays in vitro with crude cell extracts show that the biosynthetic conversion of mevalonate to squalene and the conversion of squalene to lanosterol are not impaired in the mutant cells. Gas-liquid chromatographic analyses of radioactive sterol composition after whole cell pulse experiments with [3H]squalene and with [3H]anosterol suggest that the fundamental enzymatic defect of the mutant is at the stage of lanosterol demethylation. When cells were grown in serum-free medium, lanosterol and dihydrolanosterol accumulated intracellularly in the mutant cells before cell lysis occurred; neither of these two intermediary sterols was detected in the wild-type cells grown under the same condition.

Animal Cell Mutants Defective in Sterol Metabolism: A Specific Selection Procedure and Partial Characterization of Defects

Abstract: By using a chemically defined medium, a general and highly specific procedure was devised to select for mutant cells with less abundant or structurally altered sterol in their surface membranes. Within a certain concentration range, the polyene antibiotic filipin was shown to kill only cells with normal (as opposed to decreased) membrane sterol levels. Sterol-requiring derivatives of LM cells were isolated by chemical mutagenesis, filipin treatment, and cloning followed by replica plating in soft agar. Mutants (S1 and S2) are described which, when compared to normal cells, show decreased synthesis of demosterol in vivo from acetate and mevalonate relative to cell number or to fatty acid synthesis. When exogenous sterol is supplied, mutants S1 and S2 grow normally in suspension culture. However, when deprived of sterol supplement, mutant S1 grows slower than wild type cells and mutant S2 lyses within one to two generations. Gas/liquid chromatography revealed that the mutants contained a normal spectrum of fatty acids including unsaturated fatty acyl groups but, unlike wildtype cells, they have less abundant (mutant S1) or no (mutant S2) desmosterol in either the presence or absence of exogenous cholesterol. In vitro experiments with mevalonate as the substrate suggest that the defect in both mutants is in a demethylation reaction subsequent to lanosterol synthesis. The selection method developed here may permit the isolation of mutants with defective membrane incorporation of sterols and other polyisoprenoids as well as defective synthesis of these compounds.

Sterol Requirement for Zoospore Formation in the Mosquito-Parasitizing Fungus Lagenidium Giganteum

Abstract: The oomycete Lagenidium giganteum, a facultative parasite of mosquito larvae, requires exogenous sterols for the genesis of zoospores when grown on defined or on usual mycological media. Growth med...

Sterol synthesis in relation to growth and fermentation by brewing yeasts inoculated at different concentrations

Abstract: The sterol contents of brewing yeasts harvested from an anaerobic fermentation and inoculated into air-saturated wort rise rapidly from ca. 1 mg/g dry yeast to ca. 10 mg/g and remain at this level until the oxygen is absorbed. After all oxygen is removed from the medium, sterol synthesis ceases and the concentration in the cells declines as growth occurs until a limiting value is reached, when reproductive growth ceases. In the presence of oxygen, sterols are present primarily as sterol esters; free sterols accumulate after oxygen uptake is complete. The total quantity of sterol which is synthesized in the presence of oxygen determines the extent of subsequent yeast growth. It is shown that the magnitude of sterol synthesis in the yeast population as a whole is influenced by the pitching rate.

Sterol composition and phytosterol utilization and metabolism in the milkweed bug

Abstract: Analysis of the sterols of the milkweed bug,Oncopeltus fasciatus (Dallas) and dietary sunflowerseeds revealed that there is little, if any, conversion of dietary C28 or C29 phytosterols to cholesterol in this phytophagous insect. The dietary sterols are apparently utilized with little alteration both during development to the adult stage and egg production, and cholesterol comprises <1% of the sterols in either adult males and females or in the eggs. The significance of these findings are discussed in light of the recent discovery that the C28-ecdysone, makisterone A, is the predominant molting hormone in the enbryonated egg of the milkweed bug.

Accumulation of ergosta-8,14-dien-3β-ol bySaccharomyces cerevisiae cultured with an azasterol antimycotic agent

Abstract: 15-Aza-24-methylene-D-homocholesta-8,14-dien-3β-ol, an antimycotic agent, at a concentration of 75 ng/ml inhibited ergosterol biosynthesis inSaccharomyces cerevisiae strain 3701 B resulting in the accumulation of an unusual sterol. Experimental data presented indicate that this sterol is ergosta-8,14-dien-3β-ol. The accumulation of the compound is supportive of current models of biosynthetic pathways for sterols in yeast and is consistent with inhibition by the azasterol of the Δ14 sterol reductase.

Skin surface lipids of the dog.

Abstract: The skin surface lipid of the dog has been reported to contain a high proportion of diol diesters having a lower mobility on thin layer chromatography than diesters from other species in spite of containing similar fatty acid and diol components. In the present study, dog skin surface lipid was separated by preparative thin layer chromatography into sterol esters (42%), wax diesters (32%), free sterols (9%), polar lipids (7%), and unidentified components (10%). The diesters contained 1,2-diols, each esterified with one long chain fatty acid and one isovaleric acid moiety. The diols were principally branched chain C21 and C22 compounds while the long chain fatty acids esterified with them were mainly C20 and C21 branched compounds. The fatty acids from the sterol esters were mostly saturated, branched chain C19 to C23, together with 7% of straight chain monoenoic acids, principally C21 and C22. There were only trace amounts of free sterols other than cholesterol, while the esterified sterols contained 96% cholesterol and 4% lathosterol.