Aspects of the catabolism of cholesterol to bile acids in mammals

Abstract

(1) A cholesterol-7α-hydroxylase has been investigated in rat liver cell fractions; the enzyme is located in the endoplasmic reticulum (microsomes) and requires co-factors in the cytoplasm. (2) The enzyme was assayed "by following the metabolism of cholesterol-4-14C; analysis was effected by thin layer chromatography followed by liquid scintillation counting. (3) Cholesterol-7α.-hydroxylase was found to be sensitive to prolonged homogenisation of the liver, long incubation periods, etc.; stimulation of the activity was observed only in the presence of NADPM. (4) Preliminary studies showed that the enzyme was inhibited by carbon monoxide; it appeared that a carbon monoxide binding pigment may be involved in oxygen activation for the system. The enzyme is suggested to be a mixed function oxidase. (5) The conversion of cholesterol to 7α-hydroxycholesterol can be increased several fold by preventing the reabsorption of bile salts from the gut; the significance of this enzyme as a rate-controlling enzyme in the overall catabolism to bile acids is discussed. (6) Non-enzymic oxidation of cholesterol has been investigated in some detail in order to determine whether enzymic and non-enzymic cholesterol oxidation have any common characteristics# Evidence is presented to suggest that cholesterol can be oxidised in conditions which support peroxidation of unsaturated lipids.