Monitoring hepatic cholesterol 7α-hydroxylase activity by assay of the stable bile acid intermediate 7α-hydroxy-4-cholesten-3-one in peripheral blood

Abstract

We describe an accurate method for monitoring the enzymatic activity of hepatic cholesterol 7α-hydroxylase (C7αOH; CYP7A1), the rate-limiting and major regulatory enzyme in the synthesis of bile acids. Assay of 7α-hydroxy-4-cholesten-3-one (C4), an intermediate in bile acid synthesis, revealed that the level of C4 in peripheral blood serum or plasma showed a strong correlation to the enzymatic activity of hepatic C7αOH, both at steady-state conditions (r = 0.929) as well as during the rapid changes that occur during the diurnal phases.

This assay should be of value in clarifying the regulation of bile acid synthesis in vivo in laboratory animals and humans since it allows for the monitoring of hepatic C7αOH activity using peripheral blood samples.