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Journal of Lipid Research, Vol 31, 1083-1088, Copyright © 1990 by Lipid Research, Inc.
KM Boberg, K Einarsson and I Bjorkhem
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.
ARTICLES
Apparent lack of conversion of sitosterol into C24-bile acids in humans
Institute of Clinical Biochemistry, University of Oslo, Rikshospitalet, Norway.
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