7α-Hydroxylation of cholestanol by rat liver microsomes

• Main Authors: Sarah Shefer, Susan Hauser, Erwin H. Mosbach
• Format: Article
• Language: English
• Published: Elsevier 1968-05-01
• Series: Journal of Lipid Research
• Subjects: 7α-hydroxylation; in vitro; rat liver microsomes; cholesterol; cholestanol; phenobarbital
• Online Access: http://www.sciencedirect.com/science/article/pii/S0022227520430998

In a study of the mechanism whereby 5α-bile acids are formed from cholestanol, the 7α-hydroxylation of cholestanol was investigated in rat liver preparations in vitro. It was found that in the presence of NADPH and oxygen, rat liver microsomes catalyzed the 7α-hydroxylation of cholestanol to the same extent as that of cholesterol.The rate of the hydroxylation was enhanced by prior treatment of the experimental rats with cholestyramine (a bile acid sequestrant) or by establishment of bile fistulas—i.e., by partial or complete removal of bile acids from the enterohepatic circulation. The 7-hydroxylation reaction was further stimulated by pretreatment of the animals with phenobarbital, a drug known to produce increased biosynthesis of hepatic endoplasmic membranes. The 7α-hydroxylase was inhibited by the reaction product, by sterols with 7-keto or 7β-hydroxyl groups, and also by mono- and dihydroxy bile acids of the 5β-series, although cholic acid or taurocholate produced no inhibition unless added in high concentrations.The results of these studies are in accord with the concept that the presence of a Δ5-double bond is not required for the enzymatic formation of the 7α-hydroxy derivative. The rate of this hydroxylation reaction in vitro appears to depend on the concentration of bile salts in the enterohepatic circulation of the experimental animals from whom the microsomes were obtained.