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.(ABSTRACT TRUNCATED AT 250 WORDS)
Highlights
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
(4a methyl-5a-cholest-8-en-3/3-01and 4a-methyl-5acholest-7-en-3/3-01),two lathosterols (5a-cholest-7-en-3/301 and 5a-cholest-8-en-3@-01)a,nd desmosterolin untreated gallstone patients and in gallstone patients treated with cholestyramine or chenodeoxycholic acid prior to elective cholecystectomy
The patients treated with cholestyramine had markedly increased levels of HMG-CoA reductase as compared to the controls (404k35 pmollmin per mg protein)
Summary
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, (4a, 48, 14a-trimethyl-5a-cholest-8,24-dien38-01), two dimethylsterols (4a, 4&dimethyl-5/3-cholest-8-en and 4a, 48-dimethyl-5a-cholest-82,4-dien-3#?-01), two methostenols (4a-methyl-5a-cholest-7-en-3/3a-nodl 4a-methyl5a-cholest-8-en-3/3-01),two lathosterols (5a-cholest-7-en-38-01 and 5a-cholest-8-en-3~-01a)nd desmosterol (cholest-5, 24-dien3/3-01) 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 mgkg body weight daily for 3-4 weeks, n = 8) prior to elective cholecystectomy. It is possible that the serum levels of some precursors to cholesterol may reflect the activity of the rate-limiting enzyme in cholesterol biosynthesis, HMG-CaA reductase This possibility was investigated in a more direct way in the present work by measurement of serum levels of squalene, free and esterified lanosterol, (k, 4@, 14a-trimethyl-5a-cholest-8,Z4-dien-3@-ol)t,wo dimethylsterols (4a, 4/3-dimethyl-5cr-cholest-8-en-3-aolnd 4a, 4@-dimethy1-5a-cholest-8,24-dien-3-01)t,wo methostenols (4a methyl-5a-cholest-8-en-3/3-01and 4a-methyl-5acholest-7-en-3/3-01),two lathosterols (5a-cholest-7-en-3/301 and 5a-cholest-8-en-3@-01)a,nd desmosterol (cholest-5, 24-dien-3@-01)in untreated gallstone patients and in gallstone patients treated with cholestyramine or chenodeoxycholic acid prior to elective cholecystectomy. A high correlation was obtained between the serum levels of some of the cholesterol precursors and the activity of the hepatic HMG-CoA reductase
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