title: 7 alpha-hydroxylation of 26-hydroxycholesterol, 3 beta-hydroxy-5-cholestenoic acid and 3 beta-hydroxy-5-cholenoic acid by cytochrome P-450 in pig liver microsomes.
abstract: Pig liver microsomes were found to catalyze the 7 alpha-hydroxylation of several potential bile acid precursors besides cholesterol. 26-Hydroxycholesterol, 3 beta-hydroxy-5-cholestenoic acid and 3 beta-hydroxy-5-cholenoic acid were all efficiently converted into the 7 alpha-hydroxylated products. Two cytochrome P-450 fractions showing 7 alpha-hydroxylase activity could be isolated. One fraction catalyzed 7 alpha-hydroxylation of 26-hydroxycholesterol, 3 beta-hydroxy-5-cholestenoic acid and 3 beta-hydroxy-5-cholenoic acid but was inactive towards cholesterol. The other fraction catalyzed 7 alpha-hydroxylation of cholesterol in addition to the other substrates. 26-Hydroxycholesterol in equimolar concentration did not inhibit the cholesterol 7 alpha-hydroxylase activity of this fraction. It is concluded that liver microsomes contain a cytochrome P-450 catalyzing 7 alpha-hydroxylation of 26-hydroxycholesterol, 3 beta-hydroxy-5-cholestenoic acid and 3 beta-hydroxy-5-cholenoic acid. The results indicate that this cytochrome P-450 is different from that catalyzing 7 alpha-hydroxylation of cholesterol.
authors.affiliation: Department of Pharmaceutical Biochemistry, University of Uppsala, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Toll
authors.forename: J
authors.initials: J
authors.lastname: Shoda
authors.forename: M
authors.initials: M
authors.lastname: Axelson
authors.forename: J
authors.initials: J
authors.lastname: Sjövall
authors.forename: K
authors.initials: K
authors.lastname: Wikvall
mesh_terms: D000818:Animals; D002384:Catalysis; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000378:metabolism; D002793:Cholic Acids / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000302:isolation & purification / Q000378:metabolism*; D008401:Gas Chromatography-Mass Spectrometry; D006888:Hydroxycholesterols / Q000378:metabolism*; D006900:Hydroxylation; D066298:In Vitro Techniques; D008297:Male; D008862:Microsomes, Liver / Q000201:enzymology*; D013552:Swine
chemical_list: D002793:Cholic Acids; D006888:Hydroxycholesterols; C007042:cholest-5-ene-3 beta,26-diol; C014596:3 beta-hydroxy-delta 5-cholenic acid; C029435:3-hydroxy-5-cholestenoic acid; D003577:Cytochrome P-450 Enzyme System; D002784:Cholesterol