Hepatic cholesterol and bile acid synthesis in Japanese patients with cholesterol gallstones.
In Japan the composition of gallstones is changing rapidly from the once-predominant brown-pigment stones to cholesterol ones. The present work was undertaken to clarify the mechanism of cholesterol supersaturated bile production in Japanese patients with cholesterol gallstones. In 26 non-obese and normolipidemic patients (11 with cholesterol gallstones, 8 with black- or brown-pigment gallstones, 7 without gallstones) a liver biopsy and hepatic bile were surgically obtained under standardized conditions. The cholesterol saturation of hepatic bile was significantly higher in cholesterol gallstone patients than in gallstone-free controls (195 +/- 10 vs. 146 +/- 8%, respectively; P < 0.01). The microsomal activities of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, the rate-limiting enzyme for cholesterol synthesis, cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme for bile acid synthesis, and 7 alpha-hydroxy-4-cholesten-3-one 12 alpha-hydroxylase (12 alpha-hydroxylase), the rate-limiting enzyme for cholic acid synthesis, were assayed simultaneously in the same subjects. There were positive correlations between HMG-CoA reductase and cholesterol 7 alpha-hydroxylase activities (Rs = 0.62, P < 0.005), and between cholesterol 7 alpha-hydroxylase and 12 alpha-hydroxylase activities (Rs = 0.44, P < 0.05) in all subjects, irrespective of the existence of gallstones. The activities of the three rate-limiting enzymes did not differ significantly among the three groups (cholesterol stone, pigment stone and stone-free). In conclusion, the cholesterol supersaturation of hepatic bile in nonobese and normolipidemic Japanese patients with cholesterol gallstones does not result from an increased hepatic cholesterol synthesis or a decreased bile acid synthesis.
Honda
A
A
Department of Gastroenterology, University of Tsukuba, Ibaraki, Japan.
Yoshida
T
T
Tanaka
N
N
Matsuzaki
Y
Y
He
B
B
Osuga
T
T
Kobayashi
N
N
Ozawa
K
K
D001647:Bile Acids and Salts / Q000096:biosynthesis*; D001654:Bile Pigments / Q000032:analysis; D002769:Cholelithiasis / Q000737:chemistry* / Q000378:metabolism; D002784:Cholesterol / Q000032:analysis* / Q000096:biosynthesis; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology; D008875:Middle Aged; D013253:Steroid 12-alpha-Hydroxylase / Q000378:metabolism
D001647:Bile Acids and Salts; D001654:Bile Pigments; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases; D002790:Cholesterol 7-alpha-Hydroxylase; C035248:7 alpha-hydroxy-4-cholesten-3-one-12 alpha monooxygenase; D013253:Steroid 12-alpha-Hydroxylase