Effects of 6,6-difluorocholestanol and 7,7-difluorocholestanol (cas 111300-79-9) on hepatic enzymes of cholesterol metabolism

Add time:08/29/2019    Source:sciencedirect.com

The effects of 6,6-difluorcholestanol and 7,7-difluorocholestanol (cas 111300-79-9) on enzymes of hepatic liver cholesterol were examined. Neither compound affected the activity of 3-hydroxy-3-methylglutaryl-CoA reductase. 7,7-Difluorocholestanol had no effect on the activity of acyl-CoA: cholesterol acyltransferase or cholesterol 7α-hydroxylase. However, 6,6-difluorocholestanol was a competitive substrate for cholesterol in the esterification of cholesterol catalysed by the acyltransferase. 6,6-Difluorocholestanol also inhibited hydroxylation of cholesterol by cholesterol 7α-hydroxylase but was not itself a substrate for this enzyme. These results show that substitutents in ring B of the sterol can have a significant effect on the binding of the sterol to enzymes and to the catalytic mechanism if the substituent is close to the groups in the molecule that participate.

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