scholarly journals Hydroxysteroid Dehydrogenases – Localization, Function and Regulation in the Testis

10.5772/47740 ◽  
2012 ◽  
Author(s):  
Magorzata Kotula-Balak ◽  
Anna Hejmej ◽  
Barbara Bilinsk
Keyword(s):  
Localization Function ◽  
Hydroxysteroid Dehydrogenases

scholarly journals 11β-Hydroxysteroid dehydrogenases control access of 7β,27-dihydroxycholesterol to retinoid-related orphan receptor γ

2019 ◽  
Vol 60 (9) ◽  
pp. 1535-1546 ◽  
Author(s):  
Katharina R. Beck ◽  
Silvia G. Inderbinen ◽  
Sharavan Kanagaratnam ◽  
Denise V. Kratschmar ◽  
Anton M. Jetten ◽  
...  
Keyword(s):  
Orphan Receptor ◽  
Hydroxysteroid Dehydrogenases

scholarly journals On the Importance of Clar Structures of Polybenzenoid Hydrocarbons as Revealed by the π-Contribution to the Electron Localization Function

Symmetry ◽  
2010 ◽  
Vol 2 (3) ◽  
pp. 1653-1682 ◽  
Author(s):  
Jun Zhu ◽  
Christian Dahlstrand ◽  
Joshua R. Smith ◽  
Sébastien Villaume ◽  
Henrik Ottosson
Keyword(s):  
Electron Localization Function ◽  
Electron Localization ◽  
Localization Function ◽  
Clar Structures

scholarly journals Molecular and Enzymatic Characterizations of Novel Bifunctional 3β-Hydroxysteroid Dehydrogenases/C-4 Decarboxylases fromArabidopsis thaliana

2006 ◽  
Vol 281 (37) ◽  
pp. 27264-27277 ◽  
Author(s):  
Alain Rahier ◽  
Sylvain Darnet ◽  
Florence Bouvier ◽  
Bilal Camara ◽  
Martin Bard
Keyword(s):  
Hydroxysteroid Dehydrogenases

scholarly journals Biochemical Factors Governing the Steady-State Estrone/Estradiol Ratios Catalyzed by Human 17β-Hydroxysteroid Dehydrogenases Types 1 and 2 in HEK-293 Cells

Endocrinology ◽  
2009 ◽  
Vol 150 (9) ◽  
pp. 4154-4162 ◽  
Author(s):  
Daniel P. Sherbet ◽  
Oleg L. Guryev ◽  
Mahboubeh Papari-Zareei ◽  
Dario Mizrachi ◽  
Siayareh Rambally ◽  
...  
Keyword(s):  
Nicotinamide Adenine Dinucleotide ◽  
Redox State ◽  
Nicotinamide Adenine Dinucleotide Phosphate ◽  
Glucose Deprivation ◽  
Hydroxysteroid Dehydrogenase ◽  
Structural Features ◽  
Intact Cells ◽  
Hek 293 ◽  
Hydroxysteroid Dehydrogenases ◽  
293 Cells

Abstract Human 17β-hydroxysteroid dehydrogenase types 1 and 2 (17βHSD1 and 17βHSD2) regulate estrogen potency by catalyzing the interconversion of estrone (E1) and estradiol (E2) using nicotinamide adenine dinucleotide (phosphate) cofactors NAD(P)(H). In intact cells, 17βHSD1 and 17βHSD2 establish pseudo-equilibria favoring E1 reduction or E2 oxidation, respectively. The vulnerability of these equilibrium steroid distributions to mutations and to altered intracellular cofactor abundance and redox state, however, is not known. We demonstrate that the equilibrium E2/E1 ratio achieved by 17βHSD1 in intact HEK-293 cell lines is progressively reduced from 94:6 to 10:90 after mutagenesis of R38, which interacts with the 2′-phosphate of NADP(H), and by glucose deprivation, which lowers the NADPH/NADP+ ratio. The shift to E2 oxidation parallels changes in apparent Km values for purified 17βHSD1 proteins to favor NAD(H) over NADP(H). In contrast, mutagenesis of E116 (corresponding to R38 in 17βHSD1) and changes in intracellular cofactor ratios do not alter the greater than 90:10 E1/E2 ratio catalyzed by 17βHSD2, and these mutations lower the apparent Km of recombinant 17βHSD2 for NADP(H) only less than 3-fold. We conclude that the equilibrium E1/E2 ratio maintained by human 17βHSD1 in intact cells is governed by NADPH saturation, which is strongly dependent on both R38 and high intracellular NADPH/NADP+ ratios. In contrast, the preference of 17βHSD2 for E2 oxidation strongly resists alteration by genetic and metabolic manipulations. These findings suggest that additional structural features, beyond the lack of a specific arginine residue, disfavor NADPH binding and thus support E2 oxidation by 17βHSD2 in intact cells.

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