Abstract
Hepatic cholesterol metabolism was examined in 27 Swedish patients with cholesterol gallstone disease and in 13 patients free of gallstones operated for roentgenographically suspect polyps in the gallbladder. All 40 patients underwent cholecystectomy, and a liver biopsy and gallbladder bile were obtained at surgery. The cholesterol saturation of gallbladder bile was significantly higher in patients with gallstones compared to the gallstone-free controls (131 +/- 13 vs. 75 +/- 5%, P less than 0.001). Microsomal 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase activity, governing cholesterol synthesis, did not differ between gallstone and gallstone-free patients (104 +/- 11 vs. and 109 +/- 22 pmol/min per mg protein, respectively). The activity of cholesterol 7 alpha-hydroxylase, catalyzing the catabolism of cholesterol to bile acids, was not significantly decreased in gallstone patients (6.2 +/- 1.1 vs. 8.0 +/- 2.0 pmol/min per mg protein). The capacity to esterify cholesterol, judged by the activity of acyl coenzyme A:cholesterol acyltransferase (ACAT), was similar in gallstone and gallstone-free patients (5.4 +/- 0.4 vs. 6.7 +/- 1.1 pmol/min per mg protein). In the presence of exogenous cholesterol, ACAT activity increased by more than fourfold in both groups. No correlation was found between the saturation of gallbladder bile and any of the mentioned enzyme activities in gallstone patients. It is concluded that distinct abnormalities in cholesterol metabolizing enzymes are not of major importance for development of gallstones in Swedish patients with cholesterol gallstone disease. The results support the contention that the etiology of cholesterol gallstones is multifactorial.
Highlights
Microsomal 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase activity, governing cholesterol synthesis, did not differ between gallstone and gallstone-free patients (104 f 11vs. and 109 f 22 pmol/min per mg protein, respectively)
In the group of gallstone patients cholesterol crystals were observed in gallbladder biles from 20 of the patients (75%)
The amount of bile acids seemed to be lower in bile from gallstone patients, the difference did not reach statistical significance
Summary
Microsomal 3-hydroxy-3-methylglutaryl coenzyme A (HMGCoA) reductase activity, governing cholesterol synthesis, did not differ between gallstone and gallstone-free patients (104 f 11vs. and 109 f 22 pmol/min per mg protein, respectively). The capacity to esterify cholesterol, judged by the activity of acyl coenzyme Acholesterol acyltransferase (ACAT), was similar in gallstone and gallstone-free patients (5.4 f 0.4 vs 6.7 f 1.1 pmol/min per mg protein). There is controversy as to whether HMG-CoA reductase, the rate-limiting enzyme for cholesterol biosynthesis, is increased [6,7,8,9] or unchanged [10, 11] in gallstone disease Another possibility is an inappropriate down-regulation of cholesterol 7ahydroxylase, the rate-limiting enzyme in bile acid biosynthesis [12]. In the present study these regulating enzymes of hepatic cholesterol metabolism have been assayed in subjects with and without gallstone disease. Despite highly significant increases in cholesterol concentration and saturation of "gallbladder bile in patients with gallstones, the mean values in hepatic enzyme activities did not differ from those of the controls. There is still considerable uncertainty regarding the mechanisms and regulation of cholesterol secretion into the bile
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