C,,-bile acids in humans

The metabolic fate of intravenously administered [4-14C]sitosterol was studied in two healthy subjects. In marked contrast to the results of a previous investigation with [22,233H]sitosterol, no detectable labeled Cz4-bile acid products appeared in bile. The first and rate-limiting step in the conversion of cholesterol into bile acids is catalyzed by the liver microsomal cholesterol 7a-hydroxylase. When incubated with human liver microsomes, no detectable 7a-hydroxylation of sitosterol could be demonstrated. This was the case also when using liver microsomes from two subjects treated with cholestyramine, in which case the rate of 7a-hydroxylation of cholesterol was increased threeto sixfold. In order to bypass the rate-limiting step, the metabolic fate of ’H-labeled 7a-hydroxysitostero1 was studied in two volunteers. In this case there was a significant conversion into acid products in bile (18-3276 excreted in bile during the first 17 h). Although part of the labeled products had chromatographic properties similar to those of cholic acid and chenodeoxycholic acid, further analysis showed that none of the products was identical to chenodeoxycholic acid and only traces at the most could be identical to cholic acid. Il The results suggest that healthy human subjects, in similarity with other mammalian species studied, have little or no capacity to convert sitosterol into the normal Cz4-bile acids. Boberg, K. M., K. Einarsson, and I. Bjorkhem. Apparent lack of conversion of sitosterol into CZ4-bile acids in humans. J. Lipid Res. 1990. 31: 1083-1088. Supplementary key words liver microsomes 9 ’la-hydroxylase The plant sterol sitosterol is a normal constituent of the human diet (1). It is absorbed to a limited extent in the intestine, circulates in plasma in low concentrations, and is excreted in bile. (1). In theory, the presence of an ethyl group at CZ4 should prevent or at least obstruct conversion of sitosterol into bile acids by the same mechanism as that utilized for conversion of cholesterol into (&-bile acids. In accordance with this, previous attempts to demonstrate conversion of sitosterol into normal Cp4-bile acids in rats (2) and monkeys (3) have failed. We recently showed that there is some conversion of labeled sitosterol into unusual C,,-bile acids in rats (4). The mechanism of the latter conversion must, however, be different from that involved in the conversion of cholesterol into Cp4-bile