Cortisol metabolism by human liver in vitro--IV. Metabolism of 9 alpha-fluorocortisol by human liver microsomes and cytosol.
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Abel SM, Back DJ, Maggs JL, Park BK
Cortisol metabolism by human liver in vitro--IV. Metabolism of 9 alpha-fluorocortisol by human liver microsomes and cytosol.
J Steroid Biochem Mol Biol. 1993 Dec;46(6):833-9. doi: 10.1016/0960-0760(93)90326-r.
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- 8274419 [ View in PubMed]
- 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.
