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

ABSTRACT: Cholest-8(14)-enol is the major radioactive component of the 4-di-demethyl sterol fraction biosynthesized from 4,4-dimethyl[2-(3)H(2)]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-(3)H(2)]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-(3)H(2)]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[(14)C]lanosterol as the precursor. The first step therefore in the synthesis of cholesterol from the 4,4-dimethyl[2-(3)H(2)]dienol is reduction of the Delta(14(15)) bond and not removal of the 4alpha-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.

SUBMITTER: Gibbons GF

PROVIDER: S-EPMC1168464 | biostudies-other | 1974 Oct

REPOSITORIES: biostudies-other

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Project description:The efficacy and safety of plant stanols added to food products as serum cholesterol lowering agents have been demonstrated convincingly, but their effects on cholesterol metabolism and on serum non-cholesterol sterols is less evaluated. The aim of this study was to assess the validity of serum non-cholesterol sterols and squalene as bioindices of cholesterol synthesis and absorption, and to examine how the individual serum non-cholesterol sterols respond to consumption of plant stanols.We collected all randomized, controlled plant stanol ester (STAEST) interventions in which serum cholestanol, plant sterols campesterol and sitosterol, and at least two serum cholesterol precursors had been analysed. According to these criteria, there was a total of 13 studies (total 868 subjects without lipid-lowering medication; plant stanol doses varied from 0.8 to 8.8 g/d added in esterified form; the duration of the studies varied from 4 to 52 weeks). Serum non-cholesterol sterols were assayed with gas-liquid chromatography, cholesterol synthesis with the sterol balance technique, and fractional cholesterol absorption with the dual continuous isotope feeding method.The results demonstrated that during the control and the STAEST periods, the serum plant sterol/cholesterol- and the cholestanol/cholesterol-ratios reflected fractional cholesterol absorption, and the precursor sterol/cholesterol-ratios reflected cholesterol synthesis. Plant sterol levels were dose-dependently reduced by STAEST so that 2 g of plant stanols reduced serum campesterol/cholesterol-ratio on average by 32%. Serum cholestanol/cholesterol-ratio was reduced less frequently than those of the plant sterols by STAEST, and the cholesterol precursor sterol ratios did not change consistently in the individual studies emphasizing the importance of monitoring more than one surrogate serum marker.Serum non-cholesterol sterols are valid markers of cholesterol absorption and synthesis even during cholesterol absorption inhibition with STAEST. Serum plant sterol concentrations decrease dose-dependently in response to plant stanols suggesting that the higher the plant stanol dose, the more cholesterol absorption is inhibited and the greater the reduction in LDL cholesterol level is that can be achieved.Clinical Trials Register # NCT00698256 [Eur J Nutr 2010, 49:111-117].

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

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