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Journal of Lipid Research, Vol 37, 1356-1362, Copyright © 1996 by Lipid Research, Inc.

ARTICLES

Bile acid synthesis: 7 alpha-hydroxylation of intermediates in the sterol 27-hydroxylase metabolic pathway

C Lee, KO Martin and NB Javitt
Division of Hepatic Diseases, New York University Medical Center, NY 10016, USA.

The recognition that the 7 alpha-hydroxylation of 27-hydroxycholesterol is catalyzed by an enzyme that is different from cholesterol 7 alpha- hydroxylase raises the question as to the number of similar enzymes that may be present in liver and subserve bile acid synthesis. Thus, both 3 beta-hydroxy-5-cholestenoic acid and 3 beta-hydroxy-5-cholenoic acid, further oxidation products derived from 27-hydroxycholesterol, are also 7 alpha-hydroxylated during their metabolism to chenodeoxycholic acid. Using a microsomal fraction of hamster liver and competition plot analysis, we found that the 7 alpha-hydroxylase activity for the acid substrates was approximately one-tenth that found for 27-hydroxycholesterol. Mixtures of the different substrates did not depress the total rate of 7 alpha-hydroxylation. The evidence supports the view that these substrates share the same catalytic site on a single enzyme.
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