Cytochrome b 5 augments 3β-hydroxysteroid dehydrogenase/Δ 5-Δ 4 isomerase activity
Date
2011
Authors
Goosen P.
Storbeck K.-H.
Swart A.C.
Conradie R.
Swart P.
Journal Title
Journal ISSN
Volume Title
Publisher
Abstract
During adrenal steroidogenesis the competition between 3β- hydroxysteroid dehydrogenase/Δ
5-Δ
4 isomerase (3βHSD) and cytochrome P450 17α-hydroxylase/17,20 lyase (CYP17A1) for Δ
5 steroid intermediates greatly influences steroidogenic output. Cytochrome-b
5 (Cyt-b
5), a small electron transfer hemoprotein, known to augment the lyase activity of CYP17A1, has been shown to alter the steroidogenic outcome of this competition. In this study, the influence of Cyt-b
5 on 3βHSD activity was investigated. In COS-1 cells, Cyt-b
5 was shown to significantly increase the activity of both caprine and ovine 3βHSD towards pregnenolone, 17-OH pregnenolone and dehydroepiandrosterone in a substrate and species specific manner. Furthermore, kinetic studies revealed Cyt-b
5 to have no influence on the K
m values while significantly increasing the V
max values of ovine 3βHSD for all its respective substrates. In addition, the activity of ovine 3βHSD in microsomal preparations was significantly influenced by the addition of either purified Cyt-b
5 or anti-Cyt-b
5 IgG. The results presented in this study indicate that Cyt-b
5 augments 3βHSD activity and represents the first documentation of such augmentation in any species. © 2010 Elsevier Ltd. All rights reserved.
Description
Keywords
17 hydroxypregnenolone, 3(or 17)beta hydroxysteroid dehydrogenase, cytochrome b5, prasterone, pregnenolone, steroid delta isomerase, animal cell, animal tissue, article, controlled study, enzyme activity, enzyme analysis, enzyme kinetics, enzyme purification, enzyme substrate, nonhuman, nucleotide sequence, steroidogenesis, Capra, Ovis
Citation
Journal of Steroid Biochemistry and Molecular Biology
127
05-Mar
238
247
127
05-Mar
238
247