Bile acid synthesis in man: metabolism of 7 -hydroxycholesterol- 14 C and 26-hydroxycholesterol- 3 H.

Abstract

The pathways of bile acid synthesis in man were evaluated by studying the metabolism of 7alpha-hydroxycholesterol-4-(14)C and 26-hydroxycholesterol-16, 22-(3)H administered parenterally to individuals requiring external biliary drainage. Techniques for the identification of metabolites were thin-layer chromatography, column chromatography, gas-liquid chromatography with stream splitting, and crystallization to constant specific activity. It was found that both compounds were rapidly metabolized to bile acids and excreted in bile. Of the total radioactivity recovered in bile as bile acids, 87% of the 26-hydroxycholesterol-(3)H and 90% of the 7alpha-hydroxycholesterol-(14)C was found to be metabolized to both chenodeoxycholate and cholate. Compared to 7alpha-hydroxycholesterol, a greater proportion of 26-hydroxycholesterol was found to be metabolized to chenodeoxycholate. These findings indicate that both 7alpha-hydroxycholesterol and 26-hydroxycholesterol can be intermediates in the metabolism of cholesterol to bile acids in man. The observation that conversion to cholate takes place less readily after C-26 hydroxylation is consistent with previous findings in other species.