Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET

User menu

  • My alerts
  • Log in
  • My Cart

Search

  • Advanced search
Drug Metabolism & Disposition
  • Other Publications
    • Drug Metabolism and Disposition
    • Journal of Pharmacology and Experimental Therapeutics
    • Molecular Pharmacology
    • Pharmacological Reviews
    • Pharmacology Research & Perspectives
    • ASPET
  • My alerts
  • Log in
  • My Cart
Drug Metabolism & Disposition

Advanced Search

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Special Sections
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • FAQs
    • For Subscribers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • Submit
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Research ArticleArticle

Interactions between CYP2E1 and CYP2B4: Effects on Affinity for NADPH-Cytochrome P450 Reductase and Substrate Metabolism

Cesar Kenaan, Erin V. Shea, Hsia-lien Lin, Haoming Zhang, Matthew J. Pratt-Hyatt and Paul F. Hollenberg
Drug Metabolism and Disposition January 2013, 41 (1) 101-110; DOI: https://doi.org/10.1124/dmd.112.046094
Cesar Kenaan
Chemical Biology Doctoral Program, The University of Michigan, Ann Arbor, Michigan (C.K. and P.F.H.); Department of Pharmacology, The University of Michigan Medical School, Ann Arbor, Michigan (C.K., E.V.S., H.L., H.Z. and P.F.H.); and Department of Pharmacology, Toxicology, and Therapeutics, The University of Kansas, Kansas City, Kansas (M.J.P.-H.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Erin V. Shea
Chemical Biology Doctoral Program, The University of Michigan, Ann Arbor, Michigan (C.K. and P.F.H.); Department of Pharmacology, The University of Michigan Medical School, Ann Arbor, Michigan (C.K., E.V.S., H.L., H.Z. and P.F.H.); and Department of Pharmacology, Toxicology, and Therapeutics, The University of Kansas, Kansas City, Kansas (M.J.P.-H.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Hsia-lien Lin
Chemical Biology Doctoral Program, The University of Michigan, Ann Arbor, Michigan (C.K. and P.F.H.); Department of Pharmacology, The University of Michigan Medical School, Ann Arbor, Michigan (C.K., E.V.S., H.L., H.Z. and P.F.H.); and Department of Pharmacology, Toxicology, and Therapeutics, The University of Kansas, Kansas City, Kansas (M.J.P.-H.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Haoming Zhang
Chemical Biology Doctoral Program, The University of Michigan, Ann Arbor, Michigan (C.K. and P.F.H.); Department of Pharmacology, The University of Michigan Medical School, Ann Arbor, Michigan (C.K., E.V.S., H.L., H.Z. and P.F.H.); and Department of Pharmacology, Toxicology, and Therapeutics, The University of Kansas, Kansas City, Kansas (M.J.P.-H.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Matthew J. Pratt-Hyatt
Chemical Biology Doctoral Program, The University of Michigan, Ann Arbor, Michigan (C.K. and P.F.H.); Department of Pharmacology, The University of Michigan Medical School, Ann Arbor, Michigan (C.K., E.V.S., H.L., H.Z. and P.F.H.); and Department of Pharmacology, Toxicology, and Therapeutics, The University of Kansas, Kansas City, Kansas (M.J.P.-H.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Paul F. Hollenberg
Chemical Biology Doctoral Program, The University of Michigan, Ann Arbor, Michigan (C.K. and P.F.H.); Department of Pharmacology, The University of Michigan Medical School, Ann Arbor, Michigan (C.K., E.V.S., H.L., H.Z. and P.F.H.); and Department of Pharmacology, Toxicology, and Therapeutics, The University of Kansas, Kansas City, Kansas (M.J.P.-H.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Studies in microsomal and reconstituted systems have shown that the presence of one cytochrome P450 isoform can significantly influence the catalytic activity of another isoform. In this study, we assessed whether CYP2E1 could influence the catalytic activity of CYP2B4 under steady-state turnover conditions. The results show that CYP2E1 inhibits CYP2B4-mediated metabolism of benzphetamine (BNZ) with a Ki of 0.04 µM. However, CYP2B4 is not an inhibitor of CYP2E1-mediated p-nitrophenol hydroxylation. When these inhibition studies were performed with the artificial oxidant tert-butyl hydroperoxide, CYP2E1 did not significantly inhibit CYP2B4 activity. Determinations of the apparent KM and kcat of CYP2B4 for CPR in the presence of increasing concentrations of CYP2E1 revealed a mixed inhibition of CYP2B4 by CYP2E1. At low concentrations of CYP2E1, the apparent KM of CYP2B4 for CPR increased up to 23-fold with virtually no change in the kcat for the reaction, however, at higher concentrations of CYP2E1, the apparent KM of CYP2B4 for CPR decreased to levels similar to those observed in the absence of CYP2E1 and the kcat also decreased by 11-fold. Additionally, CYP2E1 increased the apparent KM of CYP2B4 for BNZ by 8-fold and the apparent KM did not decrease to its original value when saturating concentrations of CPR were used. While the individual apparent KM values of CYP2B4 and CYP2E1 for CPR are similar, the apparent KM of CYP2E1 for CPR in the presence of CYP2B4 decreased significantly, thus suggesting that CYP2B4 enhances the affinity of CYP2E1 for CPR and this may allow CYP2E1 to out-compete CYP2B4 for CPR.

Footnotes

  • This work was supported, in part, by National Institutes of Health National Cancer Institute [Grant CA16954] and an ASPET Institutional Summer Undergraduate Research Fellowship.

  • dx.doi.org/10.1124/dmd.112.046094.

  • Received April 5, 2012.
  • Accepted October 5, 2012.
  • Copyright © 2013 by The American Society for Pharmacology and Experimental Therapeutics
View Full Text

 

DMD articles become freely available 12 months after publication, and remain freely available for 5 years. 

Non-open access articles that fall outside this five year window are available only to institutional subscribers and current ASPET members, or through the article purchase feature at the bottom of the page. 

 

  • Click here for information on institutional subscriptions.
  • Click here for information on individual ASPET membership.

 

Log in using your username and password

Forgot your user name or password?

Purchase access

You may purchase access to this article. This will require you to create an account if you don't already have one.
PreviousNext
Back to top

In this issue

Drug Metabolism and Disposition: 41 (1)
Drug Metabolism and Disposition
Vol. 41, Issue 1
1 Jan 2013
  • Table of Contents
  • Table of Contents (PDF)
  • About the Cover
  • Index by author
  • Editorial Board (PDF)
  • Front Matter (PDF)
Download PDF
Article Alerts
Sign In to Email Alerts with your Email Address
Email Article

Thank you for sharing this Drug Metabolism & Disposition article.

NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses.

Enter multiple addresses on separate lines or separate them with commas.
Interactions between CYP2E1 and CYP2B4: Effects on Affinity for NADPH-Cytochrome P450 Reductase and Substrate Metabolism
(Your Name) has forwarded a page to you from Drug Metabolism & Disposition
(Your Name) thought you would be interested in this article in Drug Metabolism & Disposition.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Citation Tools
Research ArticleArticle

CYP2E1-CYP2B4 Interactions

Cesar Kenaan, Erin V. Shea, Hsia-lien Lin, Haoming Zhang, Matthew J. Pratt-Hyatt and Paul F. Hollenberg
Drug Metabolism and Disposition January 1, 2013, 41 (1) 101-110; DOI: https://doi.org/10.1124/dmd.112.046094

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero

Share
Research ArticleArticle

CYP2E1-CYP2B4 Interactions

Cesar Kenaan, Erin V. Shea, Hsia-lien Lin, Haoming Zhang, Matthew J. Pratt-Hyatt and Paul F. Hollenberg
Drug Metabolism and Disposition January 1, 2013, 41 (1) 101-110; DOI: https://doi.org/10.1124/dmd.112.046094
del.icio.us logo Digg logo Reddit logo Twitter logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
    • Abstract
    • Introduction
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Series-Compartment Models of Hepatic Elimination
  • Warfarin PBPK Model with TMDD Mechanism
  • Identification of payload-containing catabolites of ADCs
Show more Articles

Similar Articles

Advertisement
  • Home
  • Alerts
Facebook   Twitter   LinkedIn   RSS

Navigate

  • Current Issue
  • Fast Forward by date
  • Fast Forward by section
  • Latest Articles
  • Archive
  • Search for Articles
  • Feedback
  • ASPET

More Information

  • About DMD
  • Editorial Board
  • Instructions to Authors
  • Submit a Manuscript
  • Customized Alerts
  • RSS Feeds
  • Subscriptions
  • Permissions
  • Terms & Conditions of Use

ASPET's Other Journals

  • Journal of Pharmacology and Experimental Therapeutics
  • Molecular Pharmacology
  • Pharmacological Reviews
  • Pharmacology Research & Perspectives
ISSN 1521-009X (Online)

Copyright © 2023 by the American Society for Pharmacology and Experimental Therapeutics