title: Cortisol metabolism by human liver in vitro--IV. Metabolism of 9 alpha-fluorocortisol by human liver microsomes and cytosol.
abstract: The oxidative and reductive biotransformations of 9 alpha-fluorocortisol (fluorocortisol) by human liver microsomes and cytosol have been characterized. 9 alpha-Fluorination greatly simplified cortisol metabolism in microsomes: dehydrogenation of the 11 beta-hydroxyl group and A-ring (4-ene-5 beta and 3 alpha-keto) reduction, the principle pathways, were completely blocked. Fluorocortisol was essentially metabolized by the remaining pathways, 20 beta-reduction and 6 beta-hydroxylation. In cytosol, 20 beta-reduction replaced the A-ring reduction of cortisol as the sole biotransformation. The major structure-metabolism relationships of fluorocortisol in man, i.e. complete and extensive inhibition of 11 beta-dehydrogenation and 4-ene-5 beta-reduction, respectively, were attributed to hepatic enzyme systems. Their mechanistic basis is discussed with reference to the electronic and conformational changes induced by 9 alpha-fluorination.
authors.affiliation: Department of Pharmacology & Therapeutics, University of Liverpool, England.
authors.forename: S M
authors.initials: SM
authors.lastname: Abel
authors.forename: D J
authors.initials: DJ
authors.lastname: Back
authors.forename: J L
authors.initials: JL
authors.lastname: Maggs
authors.forename: B K
authors.initials: BK
authors.lastname: Park
mesh_terms: D000328:Adult; D001711:Biotransformation; D002851:Chromatography, High Pressure Liquid; D003600:Cytosol / Q000378:metabolism; D005438:Fludrocortisone / Q000378:metabolism*; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D013058:Mass Spectrometry; D008862:Microsomes, Liver / Q000378:metabolism*; D008875:Middle Aged; D015394:Molecular Structure
chemical_list: D005438:Fludrocortisone; D006854:Hydrocortisone