Showing papers on "Lanosterol published in 1980"

In vitro and in vivo effects of the antimycotic drug ketoconazole on sterol synthesis.

Abstract: Ketoconazole, an orally active antimycotic drug, is a potent inhibitor of ergosterol biosynthesis in Candida albicans when added to culture media which support yeast or mycelial growth or to cultures containing outgrown mycelium. This inhibition coincides with accumulation of sterols with a methyl group at C-14 and can thus be attributed to an interference with one of the reactions involved in the removal of the 14 alpha-methyl group of lanosterol. When administered to rats infected with C. albicans, ketocanazole also inhibits fungal synthesis of ergosterol. A six-times-higher dose is required to effect cholesterol synthesis by rat liver.

Effect of alkyl-substituted precursors of cholesterol on artificial and natural membranes and on the viability of Mycoplasma capricolum

Abstract: Various alkyl-substituted sterols and stanols representative of the intermediates in cholesterol biosynthesis from lanosterol have been compared with respect to (a) their effect on the physical state of lecithin vesicles, (b) their efficacy as growth factors for the sterol auxotroph Mycoplasma capricolum, and (c) their effect on the physical state of the respective mycoplasma membranes. By all three criteria, sterol effectiveness progresses in the order lanosterol less than 4,4-dimethylcholestanol less than or equal to 4 beta-methylcholestanol less than 4 alpha-methylcholestanol less than cholestanol less than cholesterol. Since the corresponding steps in cholesterol biosynthesis occur in the same order, we conclude that the nuclear modifications of the lanosterol structure by oxidative demethylation serve to improve the membrane function of the sterol molecule.

Effect of plant sterols, fatty acids and lecithin on cholesterol absorption in vivo in the rat.

Abstract: The inhibitory effect of plant sterols, fatty acids and lecithin on cholesterol intestnal absorption was studied in the unanesthetized rat using a single pass perfusion technique. Bile was excluded from the perfused intestine. Cholesterol absorption did not change following the additions of cholestanol, cholestanone, lanosterol, stigmasterol and β-sitosterol. A 3-fold increase in the molarity of cholestanol and β-sitosterol or the separate additions of the saturated short and medium chain fatty acids, butyric and octanoic, also did not change cholesterol absorption. The unsaturated long chain fatty acids, oleic, linoleic, linolenic and arachidonic, inhibited cholesterol absorption. Lecithin additions at concentrations of 0.1–1.5 mM caused a progressive, dose-related inhibition of cholesterol absorption. The inhibitory effect of these agents on cholesterol absorption is likely to have been caused by changes in cholesterol solubility in the micelle and shifts in the partition coefficient of cholesterol away from the cell membrane to the micelle.

A lack of esterification of lanosterol and other methyl sterols in human serum in vitro.

Abstract: Human serum contains small amounts of free and esterified cholesterol precursors, such as lanosterol and other methyl sterols. Incubating the serum for 24 h at room temperature without and with different additions of free methyl sterols was not followed by any detectable esterification of these sterols during the subsequent 24 h incubation period, though the amount of cholesterol esters was markedly increased. [3H]dihydrolanosterol added to serum was not esterified in any lipoprotein fraction either, whereas the [14C]cholesterol added was found to be esterified during the 24 h incubation period. The lack of methyl sterol esterification in vitro suggests that these sterols are not proper substrates for serum lecithin: cholesterol acyltransferase and that esterified serum methyl sterols originate from tissues.

Lanosterol derivatives as precursors in the biosynthesis of viridin. Part 1

Abstract: 14 C-Labelled lanosterol derived from sodium [1-14C]acetate was efficiently incorporated into the aromatic-C-ring steroid viridin, confirming its derivation via a normal steroidal biosynthetic pathway. Studies with [G-3H]lanostene oxidation products were carried out to determine their relative efficiency as precursors of viridin in an attempt to identify the intermediates between lanosterol and viridin. The [G-3H]lanosterol was obtained by catalytic exchange labelling with 3H2O and principal sites of exchange in the sterol were identified by degradation experiments.

Oral contraceptives, lanosterol, and platelet hyperactivity in rat

Abstract: Lanosterol, a cholesterol precursor that increases considerably in the platelets of rats treated with oral contraceptives, was incubated with either platelet-rich plasma or washed platelet suspension. After 2 minutes there was a remarkable dose-related increase in platelet activity. This platelet hyperactivity was measured by clotting time and platelet aggregation could not be reproduced by cholesterol or ethinylestradiol.

Studies on the 14α‐Demethylation Mechanism in Cholesterol Biosynthesis

Abstract: Identification of radioactive 5 alpha-cholest-8(14)-ene-3 beta,7 alpha-diol in extracts obtained from incubations of 3 beta-hydroxy-5 alpha-[7-3H]cholest-7-ene-14 alpha-carbaldehyde with rat liver microsomes is reported. Levels of this diol in incubations of the 14 alpha-[32-3H]carbaldehyde were measured by multiple selected ion monitoring and were found to be of the same order of those of [3H]formate released from the substrate during the removal of the C-32 atom. The results demonstrate that the diol does not originate from known intermediates of cholesterol biosynthesis, i.e. 5 alpha-cholesta-7,14-dien-3 beta-ol, 5 alpha-cholest-7-en-3 beta-ol and from 5 alpha-cholest-8(14)-en-3 beta-ol. Functionalization at position 7 in the metabolism of 3 beta-hydroxy-5 alpha-cholest-7-ene-14 alpha-carbaldehyde suggests the direct involvement of the double bond in the elimination of the 14 alpha-formyl group in the biosynthetic pathway from lanosterol to cholesterol. 5 alpha-Cholest-8(14)-en-3 beta-ol appears not to be involved in the metabolism of the 14 alpha-carbaldehyde.

Phylogenetics and Biosynthesis

Abstract: The sterols of living systems are all derived by the aerobic cyclization of squalene through the intermediacy of epoxysqualene as discussed in depth elsewhere (Nes, 1977; Nes and McKean, 1977). However, epoxysqualene is not always cyclized to the same substance. Two major products (lanosterol and cycloartenol) are formed, and they are never known to be produced by cyclization in the same organism, whether the latter is unicellular or highly differentiated. This bifurcation in the steroid pathway is one of the most interesting phylogenetic markers we have, because it has no apparent influence on the structure of the functional steroid at the end of the pathway. There are two principal differences in naturally occurring, functional sterols, viz., the structure of the side chain and the double-bond character in the nucleus. Neither of these is influenced by whether lanosterol or cycloartenol is the precursor. Thus, it was shown in our laboratory (Russell et al., 1967; Raab et al.,1968; Gibbons et al., 1971) that either lanosterol or cycloartenol will yield 24-alkylsterols (sitosterol, etc.) in higher plants. Similarly, while lanosterol leads to cholesterol in animals (Tchen and Bloch, 1955), pollinastanol (14α-methyl-9,19-cyclo-5α-cholestanol, a metabolite of cycloartenol in which the Δ24 bond has been reduced and the two methyl groups at C-24 removed) has been converted to cholesterol in higher plants (Devys et al., 1969), and cycloartenol is present in red algae in which the dominant sterol is cholesterol (Ferezou et al., 1974).

Tetracyclic triterpenes. Part 5. The synthesis of epimeric 9,11-epoxides in the tri-, hexa-, and octa-norlanostane series

Abstract: Lanosterol was converted by degradation of the side chain followed by transformations within rings B and C into a series of 9,11-epoxy-7-oxo-4,4,14α-trimethylsteroids.

Generation of the onocerin system by lanosterol 2,3‐oxidosqualene cyclase ‐ implications for the cyclization process

Abstract: Der tritiierte Thioether (I) wird als Sulfidanion mit dem (+)-Bicyclofarnesylbromid (II) zum Tetraen (IIIa) alkyliert, das durch Li/Ethylamin zum Produkt (IIIb) reduziert wird.