Cholesterol precursor prevents cataracts

Abstract Previous comparisons between the Reference and Definitive Methods for measuring serum cholesterol have demonstrated a small but persistent positive bias in the Reference Method, averaging about +1.6%. Here we describe the results of further investigations designed to better characterize the nature of this bias. Analysis of a well-characterized model serum sample (SRM 909) suggests that more than half of the difference in cholesterol values determined by the two methods is the result of small contributions from cholesterol precursor sterols and phytosterols, which are also measured for the Reference Method. An additional significant contribution may be from cholesterol oxidation products, particularly 7-hydroxycholesterol isomers, which are active in the Liebermann-Burchard reaction. The 7-hydroxycholesterol in SRM 909, most of which appeared to be already present in the serum rather than formed during saponification, may account for as much as 20% of the observed difference between the methods. Contributions from other possible sources, including impurities in the cholesterol standard and incomplete saponification of cholesteryl esters, are very small. Because the observed bias is both quite small and consistent among samples, the cholesterol Reference Method continues to meet all of the requirements generally expected for a dependable and effective Reference Method.

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The metabolic sequence by which some 4,4-dimethyl sterols are converted into cholesterol

Biochemical Journal ◽

10.1042/bj1440059 ◽

1974 ◽

Vol 144 (1) ◽

pp. 59-68 ◽

Cited By ~ 19

Author(s):

Geoffrey F. Gibbons

Keyword(s):

Microsomal Fraction ◽

Soluble Fraction ◽

Sterol Fraction ◽

Methyl Groups ◽

Methyl Group ◽

Metabolic Sequence ◽

Cholesterol Precursor ◽

Fold Stimulation ◽

Better Than ◽

Stimulation Of

Cholest-8(14)-enol is the major radioactive component of the 4-di-demethyl sterol fraction biosynthesized from 4,4-dimethyl[2-3H2]cholest-8(14)-enol by rat liver microsomal fractions, and therefore the first steps in the biosynthesis of cholesterol from the latter compound probably involve removal of the 4-methyl groups. 4,4-Dimethylcholesta-8,14-dienol therefore is not an intermediate in this process, although its presence in the incubation medium at a concentration of 0.146mm almost completely inhibits the demethylation of 4,4-dimethyl[2-3H2]cholest-8(14)-enol. Nor is cholesta-8,14-dienol an intermediate in the conversion of cholest-8(14)-enol into cholest-7-enol and cholesterol. With 4,4-dimethyl[2-3H2]cholesta-8,14-dienol as the cholesterol precursor, 4,4-dimethylcholest-8(9)-enol becomes heavily labelled and there is very little radioactivity associated with cholesta-8,14-dienol.In this case, the most heavily labelled 4-di-demethyl sterols are cholest-7-enol and cholesterol with the former predominating. There is little or no radio-activity associated with cholest-8(14)-enol. A similar labelling pattern amongst the 4-di-demethyl sterols was observed with dihydro[14C]lanosterol as the precursor. The first step therefore in the synthesis of cholesterol from the 4,4-dimethyl[2-3H2]dienol is reduction of the Δ14(15) bond and not removal of the 4α-methyl group. Depending on the nature of the precursor, addition of the soluble fraction of the cell to the microsomal fraction resulted in a two- to four-fold stimulation of 4-di-demethyl sterol biosynthesis from the 4,4-dimethyl sterols studied. Under these conditions, 4,4-dimethylcholesta-8,14-dienol is the most efficient precursor of cholesterol and cholest-7-enol, and dihydrolanosterol is better than 4,4-dimethylcholest-8(14)-enol.

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Bile acid synthesis from newly synthesized vs. preformed cholesterol precursor pools in the rat

Hepatology ◽

10.1002/hep.1840170624 ◽

1993 ◽

Vol 17 (6) ◽

pp. 1095-1102 ◽

Cited By ~ 14

Author(s):

Jürgen Scheibner ◽

Michael Fuchs ◽

Michael Schiemann ◽

Gisela Tauber ◽

Erwin Hörmann ◽

...

Keyword(s):

Bile Acid ◽

Acid Synthesis ◽

Bile Acid Synthesis ◽

Cholesterol Precursor

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Biliary Lathosterol and Other Cholesterol Precursor Sterols Are Increased in Patients with Ileal Exclusion

Scandinavian Journal of Gastroenterology ◽

10.3109/00365528809093889 ◽

1988 ◽

Vol 23 (4) ◽

pp. 422-426 ◽

Cited By ~ 3

Author(s):

P. V. I. Koivisto ◽

T. A. Miettinen

Keyword(s):

Cholesterol Precursor

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Regulation of hepatic cholesterol biosynthesis. Effects of a cytochrome P-450 inhibitor on the formation and metabolism of oxygenated sterol products of lanosterol

Biochemical Journal ◽

10.1042/bj2640495 ◽

1989 ◽

Vol 264 (2) ◽

pp. 495-502 ◽

Cited By ~ 9

Author(s):

J Iglesias ◽

G F Gibbons

Keyword(s):

Reductase Activity ◽

Cholesterol Biosynthesis ◽

Mevalonic Acid ◽

Subcellular Fractions ◽

Hmg Coa Reductase ◽

Hepatocyte Cultures ◽

C 32 ◽

Lanosterol Demethylase ◽

Cholesterol Precursor ◽

Coa Reductase

The involvement of oxygenated cholesterol precursors in the regulation of 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) reductase activity was studied by examining the effect of ketoconazole on the metabolism of mevalonic acid, lanosterol and the lanosterol metabolites, lanost-8-ene-3 beta,32-diol,3 beta-hydroxylanost-8-en-32-al and 4,4-dimethylcholesta-8,14-dien-3 beta-ol, in liver subcellular fractions and hepatocyte cultures. Inhibition of cholesterol synthesis from mevalonate by ketoconazole at concentrations up to 30 microM was due exclusively to a suppression of cytochrome P-450LDM (LDM = lanosterol demethylase) activity, resulting in a decreased rate of lanosterol 14 alpha-demethylation. No enzyme after the 14 alpha-demethylase step was affected. When [14C]mevalonate was the cholesterol precursor, inhibition of cytochrome P450LDM was accompanied by the accumulation of several labelled oxygenated sterols, quantitatively the most important of which was the C-32 aldehyde derivative of lanosterol. There was no accumulation of the 24,25-oxide derivative of lanosterol, nor of the C-32 alcohol. Under these conditions the activity of HMG-CoA reductase declined. The C-32 aldehyde accumulated to a far greater extent when lanost-8-ene-3 beta,32-diol rather than mevalonate was used as the cholesterol precursor in the presence of ketoconazole. With both precursors, this accumulation was reversed at higher concentrations of ketoconazole in liver subcellular fractions. A similar reversal was not observed in hepatocyte cultures.

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