PMID: 11904232Mar 21, 2002Paper

The 11 beta-hydroxysteroid dehydrogenase type 2 activity in human placental microsomes is inactivated by zinc and the sulfhydryl modifying reagent N-ethylmaleimide

Biochimica Et Biophysica Acta
P Niu, K Yang

Abstract

Proper glucocorticoid exposure in utero is vital to normal fetal organ growth and maturation. The human placental 11 beta-hydroxysteroid dehydrogenase type 2 enzyme (11 beta-HSD2) catalyzes the unidirectional conversion of cortisol to its inert metabolite cortisone, thereby controlling fetal exposure to maternal cortisol. The present study examined the effect of zinc and the relatively specific sulfhydryl modifying reagent N-ethylmaleimide (NEM) on the activity of 11 beta-HSD2 in human placental microsomes. Enzyme activity, reflected by the rate of conversion of cortisol to cortisone, was inactivated by NEM (IC(50)=10 microM), while the activity was markedly increased by the sulfhydryl protecting reagent dithiothreitol (DTT; EC(50)=1 mM). Furthermore, DTT blocked the NEM-induced inhibition of 11 beta-HSD2 activity. Taken together, these results suggested that the sulfhydryl (SH) group(s) of the microsomal 11 beta-HSD2 may be critical for enzyme activity. Zn(2+) also inactivated enzyme activity (IC(50)=2.5 microM), but through a novel mechanism not involving the SH groups. In addition, prior incubation of human placental microsomes with NAD(+) (cofactor) but not cortisol (substrate) resulted in a concentration-dependent increase...Continue Reading

References

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Citations

Aug 7, 2003·Biochemical and Biophysical Research Communications·Atanas G AtanasovAlex Odermatt
Apr 9, 2010·The American Journal of Clinical Nutrition·Dominique RoberfroidUNKNOWN Micronutriments et Santé de la Mère et de l'Enfant Study (MISAME) Group
Feb 23, 2007·Journal of the American Society of Nephrology : JASN·Atanas G AtanasovAlex Odermatt
Mar 16, 2007·The Journal of Biological Chemistry·Danièle MontaudonPhilippe Pourquier
Aug 20, 2021·Frontiers in Endocrinology·Ifigeneia KassotakiDimitris K Grammatopoulos

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