Dehydroxylation of a 7 beta-hydroxy-C27 plant sterol in rat liver.
(22R)-Cholest-5-ene-3 beta,7 alpha,22-triol and the isomeric (22R)-cholest-5-ene-3 beta,7 beta,2-triol were 7-dehydroxylated by rat liver microsomes, after addition of NAD+ to the incubations. The product from both sterols was identified as (22R)-22-hydroxycholesta-4,6-dien-3-one by gas chromatography-mass spectrometry. The overall conversion of the 7 alpha-compound had an apparent Vmax of 5 nmol/mg protein per h, about 3-times higher than that of the 7 beta-isomer. Km was about 0.018 mmol/l in both reactions. NAD+ was required for the 7-dehydroxylation to proceed, conceivably by serving as cofactor in formation of the intermediate 7 beta,2-dihydroxy-4-cholesten-3-one. EDTA had a stimulatory effect upon the product formation. 7 alpha-Dehydroxylation of the bile acid precursor 7 alpha-hydroxy-4-cholesten-3-one has been demonstrated in liver tissue, but a 7 beta-hydroxy-C27-steroid dehydroxylating enzyme has previously not been identified. The results are discussed in relation to the marked differences in effect on neoplastic growth by the two isomeric hydroxysterols.
Boberg
K M
KM
Institute of Clinical Biochemistry, University of Oslo, Norway.
Stabursvik
A
A
Björkhem
I
I
Stokke
O
O
D000818:Animals; D002851:Chromatography, High Pressure Liquid; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006888:Hydroxycholesterols / Q000378:metabolism*; D006900:Hydroxylation; D066298:In Vitro Techniques; D008862:Microsomes, Liver / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013261:Sterols / Q000494:pharmacology
D006888:Hydroxycholesterols; D013261:Sterols; C060725:cholest-5-ene-3,7,22-triol