Selective inhibition of CYP27A1 and of chenodeoxycholic acid synthesis in cholestatic hamster liver.

Article Details

Citation

Copy to clipboard

Matsuzaki Y, Bouscarel B, Ikegami T, Honda A, Doy M, Ceryak S, Fukushima S, Yoshida S, Shoda J, Tanaka N

Selective inhibition of CYP27A1 and of chenodeoxycholic acid synthesis in cholestatic hamster liver.

Biochim Biophys Acta. 2002 Nov 20;1588(2):139-48.

PubMed ID

12385778 [ View in PubMed

]

Abstract

The aim of this study was to explore the regulation of serum cholic acid (CA)/chenodeoxycholic acid (CDCA) ratio in cholestatic hamster induced by ligation of the common bile duct for 48 h. The serum concentration of total bile acids and CA/CDCA ratio were significantly elevated, and the serum proportion of unconjugated bile acids to total bile acids was reduced in the cholestatic hamster similar to that in patients with obstructive jaundice. The hepatic CA/CDCA ratio increased from 3.6 to 11.0 (P<0.05) along with a 2.9-fold elevation in CA concentration (P<0.05) while the CDCA level remained unchanged. The hepatic mRNA and protein level as well as microsomal activity of the cholesterol 7alpha-hydroxylase, 7alpha-hydroxy-4-cholesten-3-one 12alpha-hydroxylase and 5beta-cholestane-3alpha,7alpha,12alpha-triol 25-hydroxylase were not significantly affected in cholestatic hamsters. In contrast, the mitochondrial activity and enzyme mass of the sterol 27-hydroxylase were significantly reduced, while its mRNA levels remained normal in bile duct-ligated hamster. In conclusion, bile acid biosynthetic pathway via mitochondrial sterol 27-hydroxylase was preferentially inhibited in bile duct-ligated hamsters. The suppression of CYP27A1 is, at least in part, responsible for the relative decreased production of CDCA and increased CA/CDCA ratio in the liver, bile and serum of cholestatic hamsters.

DrugBank Data that Cites this Article

Drug Enzymes

Drug	Enzyme	Kind	Organism	Pharmacological Action	Actions
Chenodeoxycholic acid	Sterol 26-hydroxylase, mitochondrial	Protein	Humans	Unknown	Substrate	Details