PMID: 8969943Nov 1, 1996Paper

The metabolism of 9 alpha-fluorinated steroids in the human kidney

Endocrine Research
S DiederichW Oelkers

Abstract

We compared the renal metabolism of 9 alpha-fluorinated steroids with that of the unfluorinated, endogenous steroid cortisol (F). By defining kinetic variables, we characterized isoenzyme activities of 11 beta-hydroxysteroid-dehydrogenase (11 beta-HSD). I) In human kidney slices, we studied the conversion of 9 alpha-fluoro-cortisol (FF) and F to their oxo-products (and vice versa). II) In human kidney microsomes, we performed the kinetic analysis of 11 beta-HSD activity for the steroid pairs F/cortisone (E) and dexamethasone (D)/11-dehydro-dexamethasone (DH-D). I) In kidney slices, FF is very weakly oxidized to 9 alpha-fluorocortisone (FE), while the reduction of FE to FF is very effective. In contrast, E is hardly reduced to F, but F is strongly inactivated to E. II) Enzyme kinetics in kidney microsomes: 1a) Oxidation of F to E: exclusively NAD-dependent; K(m) = 25.5 nmol/L. b) Reduction of E to F: clearly NADH-preferring; K(m) = 81 nmol/L; Vmax(oxidation) /Vmax(reduction) (F/E) = 26.2a) Oxidation of Dtto DH-D: exclusively NAD-dependent; K(m) = 81 nmol/L b) Reduction of DH-D to D: exclusively NADH-dependent; K(m) = 68 nmol/L; Vmax(oxidation)/Vmax(reduction) (D/DH-D) = 0.09. Thus, the equilibrium of FF/FE in human kidney slices...Continue Reading

References

Dec 1, 1990·Molecular Endocrinology·A K AgarwalP C White
Mar 1, 1968·The Biochemical Journal·I E BushR A Meigs
Nov 1, 1994·Molecular and Cellular Endocrinology·A L AlbistonZ S Krozowski
Feb 1, 1994·Steroids·F J FreyB M Frey
Mar 1, 1996·European Journal of Endocrinology·S DiederichW Oelkers

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Citations

Aug 1, 2013·Physiological Reviews·Karen ChapmanJonathan Seckl
Apr 6, 2002·American Journal of Respiratory and Critical Care Medicine·Bernadette E OrsidaE Haydn Walters
Mar 5, 2019·Metabolomics : Official Journal of the Metabolomic Society·Da-Yong HuJun-Yan Liu
Jul 27, 1999·The Journal of Steroid Biochemistry and Molecular Biology·Z KrozowskiK E Sheppard

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