HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Hepatic cholesterol and bile acid synthesis in Japanese patients with cholesterol gallstones.

Abstract
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.
AuthorsA Honda, T Yoshida, N Tanaka, Y Matsuzaki, B He, T Osuga, N Kobayashi, K Ozawa
JournalGastroenterologia Japonica (Gastroenterol Jpn) Vol. 28 Issue 3 Pg. 406-14 (Jun 1993) ISSN: 0435-1339 [Print] Japan
PMID8344502 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Bile Acids and Salts
  • Bile Pigments
  • Cytochrome P-450 Enzyme System
  • Cholesterol
  • Hydroxymethylglutaryl CoA Reductases
  • Cholesterol 7-alpha-Hydroxylase
  • 7 alpha-hydroxy-4-cholesten-3-one-12 alpha monooxygenase
  • Steroid 12-alpha-Hydroxylase
Topics
  • Bile Acids and Salts (biosynthesis)
  • Bile Pigments (analysis)
  • Cholelithiasis (chemistry, metabolism)
  • Cholesterol (analysis, biosynthesis)
  • Cholesterol 7-alpha-Hydroxylase (metabolism)
  • Cytochrome P-450 Enzyme System (metabolism)
  • Female
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Hydroxymethylglutaryl CoA Reductases (metabolism)
  • Liver (metabolism)
  • Male
  • Microsomes, Liver (enzymology)
  • Middle Aged
  • Steroid 12-alpha-Hydroxylase (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: