Influence of glutathione on the catalytic activity of reconstituted cytochrome P450 3A4

Biochemical and Biophysical Research Communications
B R Kim, D H Kim

Abstract

The role of NADPH reductase and cytochrome b5 on glutathione (GSH)-induced stimulation of P450 3A4 activity was investigated. GSH increased the Vmax of testosterone 6 beta-hydroxylation without changing the K(m) for testosterone whereas it decreased the K(m) for NADPH-P450 reductase. Addition of cytochrome b5 inhibited testosterone 6 beta-hydroxylation in the reconstituted system, depleting GSH, while it dramatically enhanced the rate of testosterone 6 beta-hydroxylation in the presence of GSH. Cumene hydroperoxide-mediated P450 3A4 activity, which is independent of NADPH-P450 reductase and cytochrome b5, was not affected by GSH. High concentration of GSH above 4 mM was inhibitory in the reconstituted systems. These results suggest that GSH increases the apparent affinity between P450 3A4 and NADPH-P450 reductase, and between P450 3A4 and cytochrome b5, but has no effect on the affinity between P450 3A4 and testosterone.

References

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Dec 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·M S ShetR W Estabrook
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Citations

Jul 15, 2015·Environmental Science and Pollution Research International·Xianai Wu, Hans-Joachim Lehmler
Jan 15, 2005·Toxicology in Vitro : an International Journal Published in Association with BIBRA·P F DehnA Thenappan
Jan 22, 2008·Archives of Biochemistry and Biophysics·Dmitri R DavydovJames R Halpert
Jun 20, 2017·Biochimica Et Biophysica Acta. Proteins and Proteomics·Julie Ducharme, Karine Auclair

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