Bile acid synthesis: 7 alpha-hydroxylation of intermediates in the sterol 27-hydroxylase metabolic pathway.
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.
Lee
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Division of Hepatic Diseases, New York University Medical Center, NY 10016, USA.
Martin
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Javitt
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NB
D000818:Animals; D001647:Bile Acids and Salts / Q000096:biosynthesis* / Q000737:chemistry / Q000302:isolation & purification; D002458:Cell Fractionation; D053493:Cholestanetriol 26-Monooxygenase; D002784:Cholesterol / Q000031:analogs & derivatives / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid; D006224:Cricetinae; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D006888:Hydroxycholesterols / Q000378:metabolism; D007700:Kinetics; D008297:Male; D008647:Mesocricetus; D008862:Microsomes, Liver / Q000201:enzymology* / Q000648:ultrastructure; D009278:Naphazoline / Q000031:analogs & derivatives / Q000494:pharmacology; D013250:Steroid Hydroxylases / Q000378:metabolism*; D013379:Substrate Specificity
D001647:Bile Acids and Salts; D006888:Hydroxycholesterols; C076996:27-hydroxycholesterol; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol; D013250:Steroid Hydroxylases; D053493:Cholestanetriol 26-Monooxygenase; D009278:Naphazoline; C038671:nafimidone