CORRELATION BETWEEN SERUM LEVELS OF SOME CHOLESTEROL PRECURSORS AND ACTIVITY OF HMG-COA REDUCTASE IN HUMAN-LIVER

  • 1 October 1987
    • journal article
    • research article
    • Vol. 28  (10) , 1137-1143
Abstract
The possibility that the serum concentrations of various cholesterol precursors may reflect the activity of the hepatic HMG-CoA reductase was investigated in humans under different conditions. The serum levels of squalene, free and esterified lanosterol, (4.alpha., 4.beta., 14.alpha.-trimethyl-5.alpha.-cholest-8,24-dien-3.beta.-ol), two dimethylsterols (4.alpha., 4.beta.-dimethyl-5.beta.-cholest-8-en-3.beta.-ol and 4.alpha., 4.beta.-dimethyl-5.alpha.-cholest-8, 24-dien-3.beta.-ol), two methostenols (4.alpha.-methyl-5.alpha.-cholest-7-en-3.beta.-ol and 4.alpha.-methyl-5.alpha.-cholest-8-en-3.beta.-ol), two lathosterols (5.alpha.-cholest-7-en-3.beta.-ol and 5.alpha.-cholest-8-en-3.beta.-ol) and desmosterol (cholest-5, 24-dien-3.beta.-ol) were measured in untreated patients (n = 7) and patients treated with cholestyramine (QuestranR, 8 g twice daily for 2-3 weeks, n = 5) or chenodeoxycholic acid (15 mg/kg body weight, daily for 3-4 weeks, n = 8) prior to elective cholecystectomy. The activity of the hepatic microsomal HMG-CoA reductase was measured in liver biopsies taken in connection with the operation. High correlations were found between the relative concentration of the precursor (.mu.g/100 mg of cholesterol) and the HMG-CoA reductase activity (pmol/min per mg of protein) in the case of free lanosterol (r = 0.93), free .DELTA.8.24-dimethylsterol (r = 0.90), free .DELTA.8-dimethylsterol (r = 0.87), free .DELTA.8-methostenol (r = 0.86), free .DELTA.7-methosterol (r = 0.86), free, esterified, and total .DELTA.8-lathosterol (r = 0.76-0.83) and .DELTA.7-lathosterol (r = 0.79-0.81). With few exceptions, the correlations were higher for the free than for the esterified sterols. Considerably lower correlations than above were found for the relative concentration of free desmosterol (r = 0.62) and squalene (r = 0.20). It is suggested that the concentration of some of the cholesterol precursors in serum may be utilized for detection of cases with increased biosynthesis of cholesterol. Among the different precursors tested, total lathosterol is particulary attractive to use in view of its easy determination by simple gas-liquid chromatography without time-consuming thin-layer chromatography.