Accumulation of 7 alpha-hydroxycholesterol in liver tissue of patients with cholesterol gallstones.

Abstract

Patients with cholesterol gallstones have a reduced pool of bile acids. This study was undertaken to clarify the mechanism by which bile acid biosynthesis does not increase to supranormal levels to cause a reexpansion of the pool. We investigated the first two steps of the bile acid biosynthesis pathway by assaying the activities of cholesterol 7 alpha-hydroxylase, the rate-limiting enzyme in this pathway, and 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase/isomerase, and by measuring the concentrations of 7 alpha-hydroxycholesterol and 7 alpha-hydroxy-4-cholesten-3-one in liver specimens from ten patients with cholesterol gallstones and ten gallstone-free controls. In the patients with gallstones, cholesterol 7 alpha-hydroxylase activity, 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase/isomerase activity, and hepatic 7 alpha-hydroxy-4-cholesten-3-one concentration did not significantly different from levels in controls, but hepatic 7 alpha-hydroxycholesterol concentration was more than twofold that of controls (12.9 +/- 2.6 vs 5.3 +/- 1.2 nmol/g liver, P < 0.01). The concentration of 7 alpha-hydroxycholesterol positively correlated with the ratio of cholesterol 7 alpha-hydroxylase activity to 3 beta-hydroxy-delta 5-C27-steroid dehydrogenase/isomerase activity (r = 0.93; P < 0.005) in the gallstone-free controls. In contrast, this correlation disappeared in the patients with gallstones. These results suggest a derangement of the normal 7 alpha-hydroxycholesterol metabolism in the patients with gallstones. The reason for the accumulation of 7 alpha-hydroxycholesterol remains unclear; however, it is possible that, in patients with cholesterol gallstone, the accumulated 7 alpha-hydroxycholesterol causes inappropriate suppression of cholesterol 7 alpha-hydroxylase activity by product inhibition.

• Authors: A Honda, T Yoshida, N Tanaka, Y Matsuzaki, B He, J Shoda, T Osuga
• Journal: Journal of gastroenterology (J Gastroenterol) Vol. 30 Issue 5 Pg. 651-6 (Oct 1995) ISSN: 0944-1174 [Print] Japan
• PMID: 8574339 (Publication Type: Journal Article)

Chemical References

• Cholestenones
• Hydroxycholesterols
• 7 alpha-hydroxy-4-cholesten-3-one
• cholest-5-en-3 beta,7 alpha-diol
• Cytochrome P-450 Enzyme System
• Cholesterol
• 3-Hydroxysteroid Dehydrogenases
• Steroid Hydroxylases
• Aryl Hydrocarbon Hydroxylases
• steroid hormone 7-alpha-hydroxylase

Topics

• 3-Hydroxysteroid Dehydrogenases (metabolism)
• Aryl Hydrocarbon Hydroxylases
• Biopsy
• Cholelithiasis (metabolism)
• Cholestenones (metabolism)
• Cholesterol (metabolism)
• Cytochrome P-450 Enzyme System (metabolism)
• Female
• Humans
• Hydroxycholesterols (metabolism)
• Liver (metabolism, pathology)
• Male
• Microsomes (metabolism)
• Middle Aged
• Steroid Hydroxylases (metabolism)