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Showing papers on "Sterol published in 1983"


Journal ArticleDOI
Konrad Bloch1
01 Jan 1983
TL;DR: In this paper, Sterol, Structure and Membrane Function (SSTF) is used to describe the structure and function of Membranes in the human brain. Critical Reviews in Biochemistry: Vol. 14, No. 1, pp. 47-92.
Abstract: (1983). Sterol, Structure and Membrane Function. Critical Reviews in Biochemistry: Vol. 14, No. 1, pp. 47-92.

635 citations


Journal ArticleDOI
TL;DR: It was demonstrated that in many species the liver is quantitatively far less important as a site for sterol synthesis than previously believed and, as a correlate of this, most sterol utilized by extrahepatic tissues is largely synthesized locally within those tissues.

407 citations


Journal ArticleDOI
TL;DR: Cultured human fibroblasts and human arterial smooth muscle cells appear to possess specific receptors for HDL that may function to facilitate cholesterol removal from cells, implying a link between the two processes.
Abstract: Cultured human skin fibroblasts and human arterial smooth muscle cells possess high-affinity binding sites specific for high density lipoproteins (HDL). Results from the present study demonstrate that binding of HDL to these sites is up-regulated in response to cholesterol loading of cells. When fibroblasts or smooth muscle cells were preincubated with nonlipoprotein cholesterol, cellular binding of 125I-HDL3 was enhanced severalfold. This enhancement was sustained in the presence of cholesterol but was readily reversed when cells were exposed to cholesterol-free medium. The stimulatory effect of cholesterol treatment was prevented by cycloheximide, suggesting the involvement of protein synthesis. Kinetic analysis of HDL3 binding showed that prior exposure to cholesterol led to an induction of high-affinity binding sites on the cell surface. In the up-regulated state, the apparent dissociation constant (Kd) of these sites was approximately 2 micrograms protein/ml. Competition studies indicated that the HDL binding sites recognized either HDL3 or HDL2 but interacted weakly with low density lipoprotein (LDL). Exposure of cells to lipoprotein cholesterol in the form of LDL also enhanced HDL binding by a process related to delivery of sterol into cells via the LDL receptor pathway. Enhancement of HDL binding to fibroblasts by either nonlipoprotein cholesterol or LDL was associated with an increased cell cholesterol content, a suppressed rate of cholesterol synthesis, decreased LDL receptor activity, and an enhanced rate of cholesterol ester formation. A comparison of HDL3 binding with the effects of HDL3 on cholesterol transport from cells revealed similar saturation profiles, implying a link between the two processes. Thus, cultured human fibroblasts and human arterial smooth muscle cells appear to possess specific receptors for HDL that may function to facilitate cholesterol removal from cells.

269 citations



Journal ArticleDOI
TL;DR: It appears that one conformer, or maybe two at high amphotericin B concentration, is responsible for the induced permeability, and from their circular dichroism spectra, these two conformers are the same in the presence of ergosterol or cholesterol.
Abstract: The selective toxicity of the polyene antibiotic amphotericin B between pathogenic eukaryotic organisms and animal cells has often been said to originate in the presence of ergosterol in fungal membranes instead of cholesterol, found in membranes of animal cells We have tested this hypothesis by measuring the proton efflux induced by amphotericin B in egg yolk phosphatidylcholine small unilamellar vesicles By measuring circular dichroism under the same conditions, we monitored the interaction of the antibiotic and its conformational changes Sterol-free vesicles are sensitive to amphotericin B, but the sensitivity of sterol-containing vesicles is always greater and increasingly so with increasing sterol concentration Ergosterol-containing vesicles are more sensitive than cholesterol-containing vesicles On the other hand, numerous amphotericin B conformers can be detected in sterol-containing vesicles, depending upon both the concentration of sterol and the amphotericin B sterol ratio It appears that one conformer, or maybe two at high amphotericin B concentration, is responsible for the induced permeability From their circular dichroism spectra, these two conformers are the same in the presence of ergosterol or cholesterol The concentration of amphotericin B necessary to obtain the two conformers is higher with cholesterol than with ergosterol, which agrees with the permeability results

139 citations


Journal ArticleDOI
TL;DR: The results imply that SCP2 enhances mitochondrial pregnenolone production by improving transfer of mitochondrial cholesterol to cytochrome P-450scc on the inner membrane, but does not directly influence the interaction of substrate with the hemoprotein.

137 citations


Journal ArticleDOI
TL;DR: regulation of activities of several membrane-bound enzymes of cholesterol metabolism in which the lipid-transfer protein and cytosolic Z-protein modulate uptake of lower-molecular-weight water-insoluble and water-soluble effectors, respectively, is discussed.

125 citations


Journal ArticleDOI
TL;DR: It is concluded that the CoA-dependent esterification rate of cholesterol is at least 60 times greater than that of beta-sitosterol.

115 citations


Journal ArticleDOI
TL;DR: Data are extended to hypothesize a role for the C-28 methyl group of ergosterol in yeast to satisfy bulk membrane and high-specificity (sparking) functions in three yeast sterol auxotrophs.

107 citations


Journal ArticleDOI
TL;DR: It is demonstrated that U18666A inhibits the reaction catalyzed by 2,3-oxidosqualene cyclase (EC 5.4.99.7), and the isoprenoid precursors are diverted not to ubiquinone as has been suggested but to squalene 2, 3:22,23-dioxide, a metabolite not on the cholesterol biosynthetic pathway.
Abstract: The relationship between cholesterol and ubiquinone synthesis in rat intestinal epithelial cell cultures was examined by using 3 beta-[2-(diethylamino)ethoxy]androst-5-en-17-one hydrochloride (U18666A). Addition of U18666A to cells caused a greater than 90% inhibition of incorporation of [3H]acetate into cholesterol and an apparent large increase in the incorporation of [3H]acetate and [3H]mevalonate into ubiquinone. However, the incorporation of 4-hydroxy[U-14C]benzoate, a ring precursor of ubiquinone, was unchanged. The apparent increase of 3H incorporation into ubiquinone was found to be due to the formation of a contaminant that has been identified as squalene 2,3:22,23-dioxide. Following incubation of cells with U18666A, its removal from the medium resulted in a decrease in squalene 2,3:22,23-dioxide labeling and a corresponding increase in the polar sterol fraction. These results demonstrate that U18666A inhibits the reaction catalyzed by 2,3-oxidosqualene cyclase (EC 5.4.99.7). As a result, the isoprenoid precursors are diverted not to ubiquinone as has been suggested but to squalene 2,3:22,23-dioxide, a metabolite not on the cholesterol biosynthetic pathway. Removal of the drug allows cyclization of squalene 2,3:22,23-dioxide, leading to formation of compounds with chromatographic properties of polar sterols.

96 citations


Journal ArticleDOI
TL;DR: This review focuses on the analysis of dietary sterol oxides in the foodstuffs examined to date with particular emphasis on isolation and characterization techniques.

Journal ArticleDOI
TL;DR: Squalene and three sterols were isolated from Nannocystis exedens (Myxobacterales) and CMevalonate was readily incorporated into the sterols.
Abstract: SUMMARY: Squalene and three sterols were isolated from Nannocystis exedens (Myxobacterales). The sterol content was about 0.4% of the dry weight; squalene content was in the same range. The main component was identified as cholest-8(9)-en-3 -ol. [14CMevalonate was readily incorporated into the sterols. The bacterium was not inhibited by nystatin or amphotericin B.

Journal ArticleDOI
TL;DR: An enzymatic assay system has been developed to measure the relative potency of fungicides such as triadimefon, triarimol, triforine, and buthiobate as inhibitors of sterol 14-demethylation.

Journal ArticleDOI
TL;DR: In both cell types the 3-hydroxy-3-methylglutaryl coenzyme A reductase activity can be suppressed by a sterol delivered to the cell in artificial nonlipoprotein form.

Journal ArticleDOI
TL;DR: It is demonstrated that marked alterations in eukaryotic membrane sterol composition was insufficient to change total phospholipid head and/or acyl group composition, and set the stage for the use of a eukARYotic cell to examine the regulation of 3-hydroxy,3-methylglutaryl coenzyme A reductase activity independent of a requirement for sterol synthesis.

Journal ArticleDOI
TL;DR: Dahl, C.E., Dahl, J.S. & Bloch, K.E. as mentioned in this paper showed that cells raised on a 1:3 mixture of ergosterol to cholesterol up to mid-logarithmic phase subsequently incorporate [1-14C]oleic acid at significantly faster rates into phospholipids than do cells grown on cholesterol alone.
Abstract: Sterol synergism as previously observed [Dahl, C.E., Dahl, J.S. & Bloch, K. (1980) Biochemistry 19, 1462-1467] and defined as a greater-than-additive growth response to pairs of sterols by Mycoplasma capricolum [Dahl, J.S., Dahl, C.E. & Bloch, K. (1981) J. Biol. Chem. 256, 87-91] is now demonstrated in the yeast mutant GL7, which is auxotrophic for sterol and unsaturated fatty acid. Mutant cells growing poorly when provided with cholesterol and oleic acid respond to ergosterol supplements (ergosterol-to-cholesterol ratio, 1:3) by a pronounced increase in growth rates and cell yields. Stigmasterol also elicits a significant synergistic effect, and 7-dehydrocholesterol, a smaller one. Evidence for a metabolic role of ergosterol in yeast membranes is presented. Cells raised on a 1:3 mixture of ergosterol to cholesterol up to midlogarithmic phase subsequently incorporate [1-14C]oleic acid at significantly faster rates into phospholipids than do cells grown on cholesterol alone.

Journal ArticleDOI
TL;DR: Analysis of lymph collections by GLC-mass spectrometry suggests that the mechanism(s) for intestinal discrimination of sterols for absorption may be independent of the mechanism for interference with efficient cholesterol uptake by the intestine.

Journal ArticleDOI
TL;DR: This previously unrecognized absolute specificity for both chirality and bulk at C-24 suggests the involvement of protein binding in at least one of the roles which sterol plays in this single-celled eukaryote.

Journal ArticleDOI
TL;DR: It is demonstrated that when hepatic cholesterol synthesis increases in response to a need for more sterol in the body, a greater proportion of biliary cholesterol is derived directly from newly synthesized sterol, but total biliaryolesterol output is unchanged, while when more cholesterol is synthesized than is needed to maintain cholesterol balance, bile acid and cholesterol output may increase.

Journal ArticleDOI
TL;DR: Responses that appear to be common in fungi treated with C-14 demethylation inhibitors were also observed in CGA-64250-treated T. deformans cells, including an increased free fatty acid content by a factor of 6.8, and higher degree of lipid unsaturation.

Journal ArticleDOI
TL;DR: The results of the present study suggest that P. japonicus larvae are probably incapable of de novo sterol synthesis but may be able to dealkylate some C28 and C29 sterols to cholesterol, which is the most effective sterol.

Journal ArticleDOI
TL;DR: The studies suggest, therefore, that the intracellular pools of cholesterol that regulate the rate of cholesterol synthesis and the rates of cholesterol esterification are functionally distinct.

Journal ArticleDOI
TL;DR: Because the concentration of Z-protein is very low in rapidly growing hepatomas, such tumors may be very poorly buffered against the effects of acyl-CoAs, free fatty acids, heme and other effectors that may vary markedly by either altered metabolism or release of metabolites from necrotic tumor tissue.

Journal ArticleDOI
TL;DR: It is concluded that 25-hydroxycholesterol increases intestinal ACAT activity, dependent upon the availability of cholesterol to the enzyme, and at cholesterol concentrations below saturation, the oxygenated sterol has a stimulatory effect.

Journal ArticleDOI
TL;DR: Growth studies with a sterol auxotrophic strain indicated that the major sterol of strain JR4, 14 alpha-methyl-ergosta-8,24(28)-dien-3 beta-ol, could satisfy "bulk" membrane requirements but not the second, structurally specific, sterol function that was defined previously.
Abstract: Genetic analysis of a nystatin-resistant sterol mutant (strain JR4) of Saccharomyces cerevisiae defective in C-14 demethylation revealed the presence of a second mutation in 5,6-desaturation. It appeared from complementation tests that a defect in delta 5-desaturase enzyme activity was required for the viability of the C-14 demethylation mutant. Growth studies with a sterol auxotrophic strain indicated that the major sterol of strain JR4, 14 alpha-methyl-ergosta-8,24(28)-dien-3 beta-ol, could satisfy "bulk" membrane requirements but not the second, structurally specific, sterol function that we defined previously (Rodriguez et al., Biochem. Biophys. Res. Commun. 106:435-441, 1982). Leakiness in the sterol mutations in strain JR4 provided a small amount of ergosterol which could satisfy this second function.

Journal ArticleDOI
TL;DR: The results imply the existence of two stereochemically distinct roles for sterol in this organism and that one of them requires, whereas the other does not require the presence of the 24 beta-methyl group.

Journal ArticleDOI
TL;DR: In this article, the chemical composition of neutral lipids which form 0.8-46.7% of five legumes (Arachis hypogea, Voandzei subterranea, Phaseolus lunatus, Lens esculentus, and Vigna sinensis) was examined for sterol, 4a-methyl sterol and triterpene alcohol fractions.
Abstract: This paper reports a study of the chemical composition of the neutral lipids which form 0.8-46.7% of five legumes (Arachis hypogea, Voandzei subterranea, Phaseolus lunatus, Lens esculentus, and Vigna sinensis). Fatty acid profiles revealed that the major acids were palmitic (13.9-31.5%) linoleic (30.9-46.4%), and oleic (5.5-40.0%). Unsaponifiable matter (1.09-3.67%) ,was examined for sterol, 4a-methyl sterol, and triterpene alcohol fractions. @-Sitosterol was the prominent component in four legumes (39.8-79.7%), while stigmasterol (41.7%) was the major component in V. sinensis. Campesterol, stigmasterol, and A5-avenasterol were detected in all samples. Among the 4a-methyl sterol fractions, obtusifoliol (9.5-39.5%), gramisterol (14.7-58.7%), and citrostadienol (8.1-47.6%) were the main components. Cycloartanol (3.0-26.4%), butyrospermol (1.4-59.1%), cycloartenol (1.4-22.4%), 24methylenecycloartano1(0.8-42%), and cyclobranol(1.0-14.4%) were the main compounds of the triterpene alcohol fractions. Leguminous seeds make an important contribution to the diet in many tropical countries. They are used as vegetables and are a good source of protein, lipid, and fatty acids for human nutrition. The fatty acid composition of the endogenous fats plays an important role in determining shelf life, nutrition, and flavor of food products. Although some values have already been presented on numerous foods (Brignoli et al., 1976) and legumes (Exler et al., 1977), data for some tropical vegetable legumes are rarely given. The nature of some Indian legume lipids was investigated by Mahadevappa and Raina (1978). Busson and Bergeret (1958) and Doku et al. (1978) have studied the chemical composition of Voandzei subterranea. A number of some tropical vegetable and subtropical vegetable oils have been analyzed for their unsaponifiable fractions, particularly sterols and methyl sterols. It was shown that campesterol, stigmasterol, @-sitosterol, A5-avenasterol, and Abtigmastenol were common constituents, @-sitosterol being the most prominent in the sterol fraction (Itoh et al., 1974a). Four sterol-containing lipid fractions were isolated from the chloroform-methanol-extracted lipids of cowpea (Vigna uguiculata) by Mahadevappa and Raina (1981). Generally 4a-methyl sterols are minor constituents of the unsaponifiable fractions and their separation from unsaponifiable matter is quite difficult. In common vegetable oils, 4a-methyl sterols were studied by Sawicki and Mordret (1970), Itoh et al. (1974b), and Jeong et al. (1975). Among the important legumes consumed in Madagascar, five of them are used commonly in this country. They are Arachis hypogea (var. Valencia), V. subterranea (or Glycine subterranea), Phaseolus lunatus (var. Inamoenus), Lens esculentus, and Vigna sinensis. Soybeans are becoming an important industrial legume for oil and protein production but are not, at this time, used very much by the population for human nutrition. This paper presents results on these five legumes consumed in Madagascar. This investigation was undertaken to obtain more information on the fatty acid composition

Journal ArticleDOI
TL;DR: Proteins which are immunochemically compatible with hepatic SCP2 appear to be present in steroidogenic tissues and may play a role in control of mitochondrial cholesterol side chain cleavage activity.

Journal ArticleDOI
TL;DR: It is concluded that during early post-natal development of the rat the ocular lens possesses the potential to satisfy about one-half of its sterol requirements from sources outside of the lens, perhaps from lipoproteins in aqueous humor.

Journal ArticleDOI
01 Sep 1983-Steroids
TL;DR: A trisulfated derivative of 24,25,26,26-tetramethyl-5 alpha-cholest-23E-ene-2 alpha, 3 beta, 6 alpha-triol (sokotrasterol sulfate) has been isolated from the sponge Halichondriidae gen. sp.