Apparent lack of conversion of sitosterol into C24-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 [22,23-3H]sitosterol, no detectable labeled C24-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 7 alpha-hydroxylase. When incubated with human liver microsomes, no detectable 7 alpha-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 7 alpha-hydroxylation of cholesterol was increased three- to sixfold. In order to bypass the rate-limiting step, the metabolic fate of 3H-labeled 7 alpha-hydroxysitosterol was studied in two volunteers. In this case there was a significant conversion into acid products in bile (18-32% 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. 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 C24-bile acids.
Boberg
K M
KM
Institute of Clinical Biochemistry, University of Oslo, Rikshospitalet, Norway.
Einarsson
K
K
Björkhem
I
I
D000328:Adult; D001647:Bile Acids and Salts / Q000378:metabolism*; D002790:Cholesterol 7-alpha-Hydroxylase / Q000378:metabolism*; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology / Q000378:metabolism*; D008875:Middle Aged; D012855:Sitosterols / Q000008:administration & dosage / Q000378:metabolism*; D013250:Steroid Hydroxylases / Q000378:metabolism*
D001647:Bile Acids and Salts; D012855:Sitosterols; D013250:Steroid Hydroxylases; D002790:Cholesterol 7-alpha-Hydroxylase