Showing papers on "Sterol published in 1974"

Beta-sitosterolemia and xanthomatosis. A newly described lipid storage disease in two sisters.

Abstract: Although the usual diet may contain 150-250 mg of plant sterols, chiefly beta-sitosterol, only trace amounts of these sterols have heretofore been found in human or animal blood and tissues. We now report elevated plant sterol levels in the blood and tissues of two sisters with extensive tendon xanthomas but normal plasma cholesterol levels. Besides beta-sitosterolemia and xanthomatosis, no other physical, mental, or biochemical abnormalities were detected.Repeatedly, the plasmas of the two sisters have contained 27.1 and 17.7 mg/100 ml of beta-sitosterol, 9.7 and 8.2 mg/100 ml of campesterol, and 0.5 and 0.5 mg/100 ml of stigmasterol, respectively. These plant sterols constituted 15.6 and 11.3% of the total plasma sterols. Some 60% of the plasma beta-sitosterol and campesterol was esterified; the measurable stigmasterol was entirely unesterified. The transport of the plasma beta-sitosterol and campesterol was largely in low density lipoproteins (76 and 83%, respectively). High density lipoproteins carried the remainder. Plant sterols were barely detectable in the very low density lipoprotein fraction. Only trace amounts of stigmasterol could be detected in the low density and high density lipoprotein fractions. The plant sterol content of the red blood cells averaged 12-13 mg/100 ml packed cells or about 13% of the total sterols. Two tendon xanthoma biopsies with the usual high concentration of cholesterol had 36.7 and 4.0 mg of plant sterols/g dry wt, of which 25.7 and 2.9 mg were beta-sitosterol, entirely in the free form. Plant sterols were also found in adipose tissue (0.2 mg/g wet wt) and in skin surface lipids (3.2 mg/g of lipid). The intestinal absorption of beta-sitosterol in both the patients, measured by two techniques, indicated greatly increased absorption of this sterol (about 24 and 28% in the patients L. H. and R. H., respectively, normal absorption being <5%). We suggest that increased absorption of beta-sitosterol must be considered as one cause of this disease. The reason for the extensive xanthomatosis in these two patients remains unknown. Perhaps in some way plant sterols initiated the development of xanthomas with otherwise normal plasma cholesterol levels. Clinical atherosclerosis has not yet occurred. The occurrence of beta-sitosterolemia in these two sisters with un-affected parents suggests an inherited recessive trait.

Inhibition of cell growth by oxygenated derivatives of cholesterol

Abstract: CELLS growing in a chemically defined, sterol-free medium must synthesise cholesterol or, in the case of L cells, desmosterol1 for membrane formation. Studies by others showed that when cholesterol or desmosterol was added to L-cell cultures the exogenous sterol was utilised and the rate of sterol synthesis was diminished, presumably by a negative feedback mechanism2,3. Our observations4, however, provide new information regarding the structures of sterols that affect sterol synthesis. Exogenous cholesterol and various metabolically related steroids do not inhibit sterol synthesis in mouse liver cell or fibroblast cultures under conditions where derivatives of cholesterol oxygenated in the 7, 20, 22 or 25 positions are highly inhibitory. These inhibitory sterols, at concentrations of 0.02–0.2 µg ml−1 specifically depress the activity of the regulatory enzyme in the sterol synthetic pathway, 3-hydroxy-3-methylgrutaryl-coenzyme A (HMG-CoA) reductase (EC 1.1.1.34), within 6 h.

Sterol to Phospholipid Molar Ratios of L Cells with Qualitative and Quantitative Variations of Cellular Sterol

Abstract: SummaryIn this study paired values of cellular sterol and phospholipid were determined after L cells were grown in medium known to induce changes in the level and kinds of cellular sterol. The sterol to phospholipid molar ratios computed from the paired values showed differences because, while the level of cellular sterol changed in response to exogenous sterol, no statistically significant differences in the levels of cellular phospholipid were apparent.When L cells were grown in the presence of concentrations of exogenous cholesterol ranging from 0 to 40 μug/ml, the sterol to phospholipid molar ratio ranged from 0.21 ± 0.01 to 0.33 ± 0.04, and, although the cellular sterol ranged from a low level almost exclusively of desmosterol (97%) to a 60% higher level almost exclusively of cholesterol (91%), no statistically significant differences were observed in the amount of cellular phospholipid. In another instance of growth in lipid-free medium a sterol to phospholipid molar ratio as low as 0.16 ± 0.03 was ...

Sterols, methylsterols, and triterpene alcohols in three Theaceae and some other vegetable oils.

Abstract: The unsaponifiables from threeTheaceae (Camellia japonica L.,Camellia Sasanqua Thunb., andThea sinensis L.) oils and alfalfa, garden balsam, and spinach seed oils and shea fat were separated into four fractions: sterols, 4-methylsterols, triterpene alcohols, and less polar compounds by thin layer chromatography. While the sterol fraction was the major one for the unsaponifiables from alfalfa and spinach seed oils, the triterpene alcohol fraction was predominant for the unsaponifiables from all other oils. The sterol, 4-methylsterol, and triterpene alcohol fractions were analyzed by gas chromatography. All the sterol fractions were alike in their compositions, consisting exclusively of Δ7-sterols, such as α-spinasterol and Δ7-stigmastenol as predominant components together with Δ7-avenasterol and 24-methylcholest-7-enol. Obtusifoliol, gramisterol (occasionally accompanied with cycloeucalenol), and citrostadienol, together with several other unidentified components, were found in the 4-methylsterol fractions from all of the oils except shea fat. The 4-methylsterol fraction from shea fat showed a characteristic composition containing a large proportion of unidentified components which had relative retention time greater than that of citrostadienol, while no citrostadienol was detected. β-Amyrin, lupeol, and butyospermol were major components of the triterpene alcohol fractions from most of the oils, but the fraction from spinach seed oil contained cycloartenol and 24-methylene-cycloartanol as predominant components. There is a close similarity in the compositions of unsaponifiables (sterols, 4-methylsterols, and triterpene alcohols) of the threeTheaceae oils. Two sterols, α-spinasterol and Δ7-stigmastenol, and five triterpene alcohols were isolated from tea seed oil. Moreover, five unidentified components beside parkeol, butyrospermol, α-amyrin, and lupeol were isolated from the triterpene alcohol fraction of shea fat.

The Intestinal Absorption of Dietary Cholesterol by Hypercholesterolemic (Type II) and Normocholesterolemic Humans

Abstract: The incomplete absorption of dietary cholesterol may represent an adaptive intestinal barrier that prevents hypercholesterolemia To explore this mechanism, we compared cholesterol absorption in 15 normocholesterolemic and 6 hypercholesterolemic (type II) subjects fed background cholesterol-free formula diets with 40% of calories as fat Each test meal consisted of a breakfast into which was incorporated scrambled egg yolk containing 300-500 mg of cholesterol and [4-(14)C]cholesterol (3-22 muCi), either naturally incorporated into the yolk cholesterol by previous isotope injection into the laying hen or added in peanut oil to the yolk of the test breakfast In some instances [1alpha-(3)H]cholesterol was the radioactive marker The radioactivity of the fecal neutral sterol fraction was determined in daily stool samples for the next 7 days to provide an estimate of unabsorbed dietary cholesterol The amount of absorbed and reexcreted labeled cholesterol proved negligible Most unabsorbed dietary cholesterol appeared in the stool on the second or third day after the meal, and 95% or more was recovered in the stool by 6 days Plasma specific activity curves were usually maximal at 48 h Normal subjects absorbed 445+/-93 (SD) of the administered cholesterol (range 259-603) Hypercholesterolemics absorbed the same percentage of cholesterol as normals: 476+/-126% (range 293-673) Absorption was similar whether the radiolabeled cholesterol was added to egg yolk or naturally incorporated in it (421+/-93 vs 489+/-98%) Six normal subjects were fed a cholesterol-free formula for 4 wk, and then different amounts of cholesterol (110-610 mg/day) were added for another 4 wk At the end of each period, single test meals containing either 110, 310, or 610 mg of cholesterol and [1alpha-(3)H]cholesterol were administered Cholesterol absorption was 423+/-60% and 454+/-83% for the two dietary periods, respectively The absolute cholesterol absorption was linearly related to the amount of cholesterol in the test meal, and absorption was not affected by background diets high or low in cholesterol content

Effect of light intensity upon lipid composition ofNitzschia closterium (Cylindrotheca fusiformis)

Abstract: Total fatty acid, total sterol, fatty acids of specific lipid classes, and unsaturated fatty acids produced inNitzschia closterium were compared qualitatively and quantitatively as a function of changes in light intensity. Increased levels of total fatty acids were observed in cells grown at high light intensity when compared to cells grown at low light intensity. However, the percentage of unsaturated fatty acid decreased under high light conditions. Fatty acid analysis of triglyceride and 1,3 diglyceride fractions indicated an increase in levels of fatty acid at high light intensity when compared to low light intensity, while levels of polar lipid fatty acids increased at low light intensity. These analyses can be taken to indicate an increase in triglyceride and diglyceride at high light and a decrease in polar lipid at high light. Levels of free fatty acids did not differ significantly with light intensity. The levels of total sterol also were unaffected by changes in light intensity. However, levels of sterol isolated as free sterol and sterol associated in a yet unknown manner in the polar lipid fraction varied with changes in light intensity. Levels of polar lipid sterol increased at high light intensity compared to low light intensity, while the opposite was true for free sterol. The greatest percentage of total sterol was found in the polar lipid class regardless of light intensity.

Molecular Basis for the Selective Toxicity of Amphotericin B for Yeast and Filipin for Animal Cells

Abstract: Among the polyene antibiotics, many, like filipin, cannot be used clinically because they are toxic; amphotericin B, however, is useful in therapy of human fungal infections because it is less toxic. Both the toxicity of filipin and the therapeutic value of amphotericin B can be rationalized at the cellular and molecular level by the following observations: (i) these polyene antibiotics showed differential effects on cells; filipin was more potent in lysing human red blood cells, whereas amphotericin B was more potent in inhibiting yeast cell growth; and (ii) the effects of filipin were more efficiently inhibited by added cholesterol, the major membrane sterol in human cells, whereas the effects of amphotericin B were more efficiently inhibited by ergosterol, the major membrane sterol in yeast. The simplest inference is that the toxicity and effectiveness of polyenes are determined by their relative avidities for the predominant sterol in cell membranes.

Resistance to Polyene Antibiotics and Correlated Sterol Changes in Two Isolates of Candida tropicalis from a Patient with an Amphotericin B-resistant Funguria

Abstract: Two isolates of Candida tropicalis resistant to amphotericin B were obtained from a patient with pyelonephritis due to Candida. Isolate Ri showed a twofold increase in resistance to amphotericin and to nystatin when compared with two sensitive strains of C. tropicalis and one of Candida albicans. Isolate R2 was extremely resistant to amphotericin B, etruscomycin, and nystatin. The sterols of R1, R2, and the sensitive strains of Candida were compared qualitatively by ultraviolet spectrophotometry, thin-layer chromatography, gas-liquid chromatography, and the Liebermann-Burchard reaction. Both polyene-resistant isolates had altered sterols. R1 contained an unidentified A5,7 sterol and little, if any, ergosterol; R2 was totally lacking in A5,7 sterols. Chromatographic analyses showed that R2 had three sterols that were distinguishable from lanosterol. It is concluded that the resistance of isolates R1 and R2 to polyene antibiotics is a consequence of their altered sterol composition.

Effect of insulin on sterol and fatty acid synthesis and hydroxymethylglutaryl CoA reductase activity in mammalian cells grown in culture.

Abstract: The effects of insulin on the synthesis of sterols and fatty acids and on the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.34), a rate-limiting enzyme for sterol synthesis, were studied in mammalian cells grown in culture. While in some established cell lines sterol synthesis was not affected significantly by the hormone, in the nonpermanent human and animal cells the synthesis of lipids, especially that of sterols, as well as the activity of the reductase were stimulated following an incubation with insulin in a medium containing serum albumin for a few hours or longer. These effects of insulin were also demonstrable in the presence of solvent-extracted serum, which itself increases sterol synthesis and reductase activity. In medium containing whole serum insulin was ineffective. Addition of glucose decreased sterol synthesis as well as reductase activity. The effects of insulin were prevented by cycloheximide and are probably due to an increased synthesis of 3-hydroxy-3-methylglutaryl CoA reductase or of a protein that regulates its activity.

Sterol molecular modifications influencing membrane permeability.

Abstract: Various sterols and related steroids were tested for their ability to influence ethanol-induced electrolyte leakage from Hordeum vulgare roots. Cholesterol had the greatest influence and, depending on concentration, it stimulated or inhibited the loss of electrolyte. Cholesterol, however, was ineffective if the roots were pretreated with ethanol. These data suggest that sterols protect rather than restore membrane structure. First, modifications in the cholesterol perhydrocyclopentanophenanthrene ring system suggest that at least one double bond is required for membrane activity. Second, increasing the bulkiness of the C(17) side chain of cholesterol, as shown with campesterol, stigmasterol, and sitosterol, decreased its activity. Apparently for maximum effectiveness the sterol molecule should have a relatively flat configuration. Third, the C(3)-hydroxyl group is required for membrane activity since cholesteryl methyl ether, cholest-5-ene-3beta-thiol and cholesteryl halogens were without activity. Exception to the foregoing rule was cholestane which was slightly active but which has neither a C(3)-hydroxyl group nor a double bond in the ring system.

Analysis of methylsterol fractions from twenty vegetable oils.

Abstract: The unsaponifiables separated from 20 vegetable oils were divided into sterol and three other (less polar compound, triterpene alcohol, and 4-methylsterol) fractions by preparative thin layer chromatography. The amounts of the sterol fractions were more than ca. 30% in the unsaponifiables from all of the oils, except tohaku, pumpkin seed, and fagara seed oils. Composition of the sterol fractions were determined by gas liquid chromatography. Individual components of the sterol fractions were identified by gas liquid chromatography and combined gas liquid chromatography-mass spectrometry. β-Sitosterol was found as the most predominant component in the sterol fractions from all oils, except two, i.e. the sterol fraction from pumpkin seed oil contained no detectable amount of β-sitosterol and the sterol fraction from akamegashiwa oil contained Δ5-avenasterol as the most abundant component. Campesterol, stigmasterol, Δ5-avenasterol, Δ7-stigmastenol, and Δ7-avenasterol and also trace amounts (at the very least) of cholesterol and brassicasterol were found in most of the oils analyzed. It may be noted that a large amount (ca. 9%) of cholesterol was detected in the sterol fraction from capsicum seed oil. The presence of 24-methylenecholesterol and Δ5-avenasterol in the sterol fraction of akamegashiwa oil was demonstrated by isolation of these sterols.

Plant growth retardants as inhibitors of sterol biosynthesis in tobacco seedlings.

Abstract: Three plant-growth retardants 2′-isopropy1-4′-(trimethylammonium chloride)-5-methylphenylpiperidine carboxylate (Amo 1618), β-chloroethyltrimethylammonium chloride, and tributyl-2, 4-dichlorobenzylphosphonium chloride were tested for their effects on sterol production in, and growth of tobacco (Nicotiana tabacum) seedlings. As the concentration of each retardant increased, there was an increased inhibition of the incorporation of dl-2-14C-mevalonic acid into sterol (particularly desmethylsterol) fractions and an increased retardation of stem growth. Growth retardation was observed with both single and repeated retardant treatments, and with Amo 1618, in particular, a close quantitative relationship between inhibition of sterol biosynthesis and stem growth was obtained. Gibberellic acid completely overcame retardant effects and application of sterols also restored normal growth. It is concluded that the concept of causality in the relationship between growth retardation and gibberellin biosynthesis is probably premature, since growth retardants have a more general inhibitory action on isoprenoid biosynthesis in plants.

Cholesterol metabolism in anorexia nervosa and hypercholesterolemia.

Abstract: Fecal bile acid and neutral sterol excretion were measured in 4 girls with anorexia nervosa using the chemical sterol balance technique. Bile acid excretion was markedly reduced in 2 (30 and 65 mg/day) in whom the plasma cholesterol concentrations were respectively 410 and 370 mg/100 ml. In the 2 other girls whose plasma cholesterol concentrations were 230 and 265 mg/100 ml daily bile acid outputs were 197 mg and 100 mg (normal range). In the 3 girls with hypercholesterolemia, the daily intake of cholesterol exceeded the total fecal excretion of steroids, indicating that dietary cholesterol was being retained. One subject was restudied when she had regained lost weight. Her plasma cholesterol had fallen from 410 to 225 mg/100 ml, bile acid excretion had risen from 30 to 153 mg/day and the sterol balance had changed from a retention of 189 mg to a net excretion of 655 mg/day. Hypercholesterolemia in anorexia nervosa may reflect diminished cholesterol and bile acid turnover which may result from re...