Showing papers on "Lanosterol published in 1969"
TL;DR: The transformation of 2,3-oxidosqualene to lanosterol is catalyzed by a microsomal enzyme (cyclase) which can be obtained in soluble and partially purified form by treatment of liver microsomes with deoxycholate as previously shown.
Abstract: The transformation of 2,3-oxidosqualene to lanosterol is catalyzed by a microsomal enzyme (cyclase) which can be obtained in soluble and partially purified form by treatment of liver microsomes with deoxycholate as previously shown. The catalytic and physical properties of the soluble enzyme are determined by ionic strength. In 0.4 M KCl the cyclase exists largely in a dissociated, enzymatically active form. Solutions of low ionic strength (0.1 M KCl or less) cause enzyme aggregation and loss of activity. The anionic detergent deoxycholate is essential for cyclase activity, but is effective only in a narrow concentration range.
47 citations
TL;DR: It is concluded that cycloartenol is a true phytosterol precursor in the tissue cultures, whereas the possible role of lanosterol (not detectable in the cultures, even by isotopic dilution experiments) is not proven.
Abstract: Tissue cultures of Nicotiana tabacum were treated with [14C]cyeloartenol and [14C]lanosterol, and the 4,4-dimethylsterol 4-methylsterol and phytosterol fractions were examined for radioactivity. In both cases activity was incorporated into the phytosterols.
The distributions of radioactivity in the 4,4-dimethylsterols and 4-methylsterols were compared with those obtained by incorporation of [14C]acetic acid. It is concluded that cycloartenol is a true phytosterol precursor in the tissue cultures, whereas the possible role of lanosterol (not detectable in the cultures, even by isotopic dilution experiments) is not proven.
41 citations
TL;DR: To study the involvement of 93-1 9-cyclopropane sterols in phytosterol biosynthesis, the conversion of 24-methylene, cycloartenol, and [2-3H2]lanosterol into poriferasterol by the phytoflagellate Ochromonas malhamens8s is examined.
Abstract: rence of cycloartenol (I) and 24-methylenecycloartanol (III) in plants and their rapid labelling from [2-14C]mevalonate and [1-14C]acetate under conditions where phytosterols are being actively synthesized (see references above). To study the involvement of 93-1 9-cyclopropane sterols in phytosterol biosynthesis we have now examined the conversion of 24-methylene[2-3H2]cycloartanol, [2 3H2]cycloartenol, [2 3H2]Cycloartenone and [2-3H2]lanosterol into poriferasterol (IV) by the phytoflagellate Ochromonas malhamens8s. Experimental and results. Lanosterol, cycloartenol and 24-methylenecycloartanol, purified by t.l.c. on AgNO3-impregnated silica gel, were converted into the corresponding 3-ketones by chromic acid oxidation and then labelled with 3H at C-2 by exchange on a basic alumina column that
27 citations
25 citations
TL;DR: In this paper, the trimethylsilyl ethers of sterols in the free and ester fractions were analyzed by gas chromatography-mass spectrometry and showed that cholesterol and lathosterol made up 93% of the total sterols and were the predominating sterols.
Abstract: Lipid extracts of human meconium were separated by chromatography on silicic acid and lipophilic Sephadex. Trimethylsilyl ethers of sterols in the free and ester fractions were analyzed by gas chromatography-mass spectrometry. Cholesterol and lathosterol made up 93% of the total sterols and were the predominating sterols in the unesterified fraction (relative abundance: 96%). The remaining 4% in this fraction consisted of lanosterol, 24,25-dihydro-Δ8-lanosterol, 24,25-dihydro-Δ9-lanosterol, 4α,14α-dimethyl-5α-cholest-7 (and 8)-en-3β-ol, and Δ7- and Δ8-methostenol. The sterol ester fraction contained 4,4-dimethyl-5α-cholest-8-en-3β-ol, 4,4-dimethyl-5α-cholest-8,14-dien-3β-ol, β-sitostanol, cholesterol, lathoesterol, lanosterol, 24,25-dihydro-Δ8-lanosterol, 4α,14α-dimethyl-5α-cholest-7(and 8)-en-3β, and Δ7- and Δ8-methostenol. However, this fraction contained a smaller proportion of Δ7-sterols than the free fraction. The percentage of cholesterol and lathosterol was also relatively smaller (75%) than in the free sterol fraction.
23 citations
20 citations
TL;DR: The transterminal methyls of squalene derive from C-2 of mevalonic acid, and the conversion of this methyl group into 2,3-oxide and lanosterol occurs without interchange of isopropylidene methyls as mentioned in this paper.
Abstract: The trans-terminal methyls of squalene derive from C-2 of mevalonic acid, and the conversion of squalene in turn into squalene 2,3-oxide and lanosterol occurs without interchange of isopropylidene methyls, so that C-2 of mevalonic acid provides the 4α-methyl group of lanosterol.
19 citations
TL;DR: A cell-free enzyme preparation from Phycomyces blakesleeanus is described which catalysed the cyclization of the [ 14C]squalene-2,3-oxide to [14C]lanosterol.
18 citations
TL;DR: Tissue cultures of Nicotiana tabacum were incubated anaerobically with [14C]-2,3-oxidosqualene and radioactive triterpenes were isolated by extraction, alcaline hydrolysis and chromatography, and radioactivity was found to be present in cycloartenol and 24-methylene-cyclOartenol, but no radioactivity could be detected in lanosterol.
Abstract: Tissue cultures of Nicotiana tabacum were incubated anaerobically with [14C]-2,3-oxidosqualene and radioactive triterpenes were isolated by extraction, alcaline hydrolysis and chromatography. After acetylation and epoxidation, the radioactivity was found to be present in cycloartenol and 24-methylene-cycloartenol, but no radioactivity could be detected in lanosterol.
16 citations
TL;DR: Squalene 2,3-oxide lanosterol cyclase selectively converts the 1′-cismethyl isomer as a component in a mixture of cis- and trans-1-methylsqualene2,3oxides into 4α-ethyl-4β,14α-dimethylcholesta-8,24-dien-3β-ol as mentioned in this paper.
Abstract: Squalene 2,3-oxide lanosterol cyclase selectively converts the 1′-cis-methyl isomer as a component in a mixture of cis- and trans-1-methylsqualene 2,3-oxides into 4α-ethyl-4β,14α-dimethylcholesta-8,24-dien-3β-ol.
14 citations
TL;DR: The chapter describes assay based on that employed by Steinberg, Avigan, and Goodman for reduction of desmosterol or lanosterol, and discusses its properties, substrate specificity, susceptibility to specific inhibitors, and role in sterol biogenesis.
Abstract: Publisher Summary The biological reduction of desmosterol is readily demonstrated in the rat by injecting the labeled sterol intraportally and isolating radioactive cholesterol from the liver. The 24,25-double bond in a variety of sterols can be reduced by the same enzyme, and the more general name “sterol Δ - 24 -reductase” is more appropriate. Until the enzyme is solubilized and purified, it should be recognized that the name refers only to activities demonstrable in particulate preparations. As the substrates are added in suspension, little can be said with respect to kinetics or intimate mechanism of action of the enzyme. This chapter discusses its properties, substrate specificity, susceptibility to specific inhibitors, and role in sterol biogenesis. The chapter describes assay based on that employed by Steinberg, Avigan, and Goodman for reduction of desmosterol or lanosterol.
TL;DR: The results indicate that cholesterol and minor amounts of desmosterol, Δ7-cholestenol, lanosterol, dihydrolanosterols, dehydromethostenol and possibly ergosterol were present in the bovine tissues.
Abstract: Thin layer and gas liquid chromatography, (GLC) were employed as complementary techniques to investigate naturally-occurring steroids in the unsaponifiable matter of bovine muscle and adipose tissue. Three GLC liquid phases, differing in selective partition properties, were used to effectively identify unknown steroids. The results indicate that cholesterol and minor amounts of desmosterol, Δ7-cholestenol, lanosterol, dihydrolanosterol, dehydromethostenol, Δ8-methostenol, Δ7-methostenol, cholestanol and possibly ergosterol were present in the bovine tissues. The minor steroids, with the exception of cholestanol and ergosterol, are steroid precursors in cholesterol biosynthesis. Common hormonal steroids were not found in the unsaponifiables of the tissues.
TL;DR: The results show that cholesterol synthesis from labeled acetate is noticeably inhibited by BBA final concentrations as small as 10 μM, while the rate of labeling is much less inhibited by HBBA, and indicate that BBA probably affects some of the reactions which lead acetate to mevalonate formation.
Abstract: Cholesterol biosynthesis has been examined using rat liver slices in vitro from 2-14C-acetate and 2-14C-mevalonate, in the presence of β-benzal butyric acid (BBA) and its metabolite, α-hydroxy β-benzal butyric acid (HBBA), both of which are postulated to act as potential hypocholesterolemic agents. Procedures have been devised to follow radioactivity incorporation of these precursors into the squalene, lanosterol and cholesterol fractions. The results show that cholesterol synthesis from labeled acetate is noticeably inhibited by BBA final concentrations as small as 10 μM, while the rate of labeling is much less inhibited by HBBA. When acetate is replaced by labeled mevalonate, cholesterol synthesis is hardly inhibited by both BBA and HBBA. The results indicate that BBA probably affects some of the reactions which lead acetate to mevalonate formation. Acetyl-CoA: ligase (E.C.6.2.1.1) and acetyl-CoA acetyl transferase (E.C.2.3.1.) therefore have been examined. Ligase activity is substantially inhibited only by 1 mM concentration of BBA and HBBA, whereas the transferase enzyme is unaffected. BBA probably affects other reactions in the metabolic sequence which converts acetate into mevalonate.
TL;DR: In the absence of iodine, photolysis of 3β-Acetoxy and 3βbenzoyloxy-lanost-24-en-11β-ol nitrites on photolyis in the presence of iodine gave 19-iodo-derivatives.
Abstract: 3β-Acetoxy- and 3β-benzoyloxy-lanost-24-en-11β-ol nitrites, readily available from lanosterol, on photolyis in the presence of iodine give 19-iodo-derivatives. By further transformations cycloartenol has been obtained. The formal total synthesis of this latter compound is, therefore, complete. Photolysis of the above mentioned nitrites in the absence of iodine gives the corresponding 19-oximino- and thence 19-cyano-derivatives. Such derivatives have not, so far, been converted into cycloartenol.
TL;DR: In this article, it was shown that the absence of an entire isoprenoid unit from the non-oxidized terminus of squalene oxide does not prevent normal biochemical cyclization.
Abstract: SUBSEQUENT to the finding that squalene 2,3-oxide is a general intermediate in the enzymic conversion of squalene into lanosterol and other 3-hydroxylated sterols, the transformation of structurally modified squalene oxides into sterol-like products was first reported from these laboratories.' In that preliminary study, the effect on side-chain reduction and shortening was tested and found not to deter seriously the biological cyclization process. In extending this approach, we have now determined that the absence of an entire isoprenoid unit from the non-oxidized terminus of squalene oxide does not prevent normal biochemical cyclization : constant. Another portion of the crude sterol product was silylated with trimethylsilyl chloride in pyridine and subjected to fractionation by preparative g.1.c. (5% diethyleneglycol succinate a t 190\"), 47% of the radioactivity appearing in a single peak having the same retention time (Rcholestane 0.71) as the trimethylsilyl ether of authentic (11). The radioactive silyl ether was collected, hydrolysed with ethanolic KOH, and subjected to preparative g.1.c. on an XE-60 column at 180\"; 91% of the activity was found in a fraction with the same retention time (Rcholestane 1-90) as authentic (11).
TL;DR: Experimental uncertainties did not permit the conclusion that the asymmetrically labelled squalene might have been cyclized preferentially from one end, and a certain inequality of labelling was indicated.
Abstract: Lanosterol was biosynthesized in pig liver homogenate from [4,8,12-(14)C(3)]farnesyl pyrophosphate and [4S-4-(3)H]NADPH through the intermediary formation of squalene labelled asymmetrically with (3)H. The biosynthetic lanosterol, freed from labelled 24,25-dihydrolanosterol, which was also synthesized, was converted into 24,25-dihydrolanosteryl acetate and subjected to chemical degradations to locate the position(s) of the (3)H label in the molecule. The ratio of (3)H at C-11 to that at C-12 was found to be 1.28. Although a certain inequality of labelling was thus indicated, experimental uncertainties did not permit the conclusion that the asymmetrically labelled squalene might have been cyclized preferentially from one end.
TL;DR: The absolute configuration at C23 in the naturally occurring 23-hydroxylanosterol has been deduced to be S, and in its C23 epimer to be R, by correlation of their molecular rotations and that of lanosterol with those of R(−) and S(+) 4-methylpent-3-en-2-ol.
TL;DR: The results indicate that α-methyl γ-phenyl butyric acid probably affects some of the enzymic reactions which convert acetate into mevalonate and meval onate into squalene, without influencing successive metabolic steps.
TL;DR: In the biosynthesis of lanosterol, the 4α-methyl group is derived from C-2 of mevalonic acid as discussed by the authors, which is the same as the C-1 of the mevalone.
Abstract: In the biosynthesis of lanosterol the 4α-methyl group is derived from C-2 of mevalonic acid.
Patent•
14 Oct 1969
TL;DR: In this paper, the authors describe a new class of cholesteric and SMECTIC LIQUID CRYSTALS, which are called 9,19-CYCLOPROPANE TRITERPENES.
Abstract: THE CHEMICAL SYNTHESIS AND ISOLATION FROM NATURAL SOURCES OF A NEW CLASS OF CHOLESTERIC AND SMECTIC LIQUID CRYSTALS ARE DESCRIBED. THESE CONSIST OF VARIOUS FATTY ACID ESTERS OF TETRACYLIC TRIERTENES INCLUDING MEMBERS OF THE CLASS OF 9,19-CYCLOPROPANE TRITERPENES. THESE TRITERPENES INCLUDE 9,19-CYCLOLANOST-24-EN-3B-OL(CYCLOARTENOL), 4A,14A,24B-TRIMETHYL-9,19-CYCLOCHOLESTAN-3B-OL, 24E-METHYL-9,19-CYCLOLANOSTAN-3B-OL(24E-METHYL CYCLOARTANOL) AND 24-DIHYDRO LANOSTEROL AND ALL CHEMICALLY RELATED PRODUCTS.
TL;DR: The 3β-amino analogues of cycloartenol, lanosterol and their 24,25-dihydro compounds have been prepared by sodium reduction of the corresponding 3-oximes and further characterized by their N-acetyl and N-salicylidene derivatives as discussed by the authors.
TL;DR: Synthetic panaxadiol monoside possesses a higher physiological activity than the original panaxadsine and is capable of glycosylating diatomic triterpenic alcohols.
Abstract: The synthesis of lanosterol,β-sitosterol, cholesterol, and panaxadiolβ-glycosides was accomplished. The feasibility of glycosylating diatomic triterpenic alcohols was demonstrated with panaxadiol. The glycosylation ofβ-sitosterol and cholesterol is accompanied by the formation of di-β-sitosterol and dicholesterol ethers. Synthetic panaxadiol monoside possesses a higher physiological activity than the original panaxadiol.
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TL;DR: In this article, the results of studies focusing on steroids were discussed, and the successful use of 6-vinyl-2-picoline as a bisannelating agent in the preparation of tricyclic dienone 4 from cyclohexanone was reported.
Abstract: Publisher Summary This chapter discusses results of studies focusing on steroids. The biological significance of epoxysqualene in sterol biosynthesis was affirmed by its conversion to fusidic acid, yeast sterolst, and by the annelation of modified squalene oxide precursors. In the transformation of lanosterol to cholesterol, evidence accumulated that the removal of the C-14 methyl group involves the loss of the 15α hydrogen atom and that the loss of the 4α and not the 4β-methyl occurs first. The configuration of the hydrogens gained or lost at carbon atoms 5 to 9 in the migration of the double bond at the C-8 to the C-5 position in the conversion of lanosterol to cholesterol was the subject of several communications. The stereochemistry of the hydrogen atoms involved in the introduction of the C-24 alkyl groups in phytosterols was also investigated. Developments in the total and partial synthesis of steroidal estrogens and heterocycles were reviewed. Interesting approaches to the construction of carbocyclic systems were discussed. The successful use of 6-vinyl-2-picoline as a bisannelating agent in the preparation of the tricyclic dienone 4 from cyclohexanone was also reported.