Skip to main content

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • Archive
  • Information
    • Instructions to Authors
    • Submit a Manuscript
    • For Subscribers
    • For Advertisers
    • Terms & Conditions of Use
    • Permissions
  • Editorial Board
  • Alerts
    • Alerts
    • RSS Feeds
  • Virtual Issues
  • Feedback
  • 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

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
Drug Metabolism & Disposition

Advanced Search

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

N-hydroxylation of the antiprotozoal drug pentamidine catalyzed by rabbit liver cytochrome P-450 2C3 or human liver microsomes, microsomal retroreduction, and further oxidative transformation of the formed amidoximes. Possible relationship to the biological oxidation of arginine to NG-hydroxyarginine, citrulline, and nitric oxide.

B Clement and F Jung
Drug Metabolism and Disposition May 1994, 22 (3) 486-497;
B Clement
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
F Jung
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • Article
  • Info & Metrics
  • eLetters
  • PDF
Loading

Abstract

Previous investigations have shown that the antiprotozoal drug pentamidine is N-hydroxylated by rabbit and rat liver microsomal fractions. Indirect evidence for the participation of the cytochrome P-450 enzyme system was obtained. In this study, rabbit liver cytochrome P-450 2C3 is shown by reconstitution experiments with highly purified variants of P-450 2C3 isolated from rabbit liver and purified variants of P-450 2C3 expressed by recombinant Escherichia coli to be a microsomal pentamidine N-hydroxylase. The two variants, P-450 2C3 (6 beta H) and P-450 2C3 (6 beta L), are equally efficient for the formation of the monoamidoxime derivative of pentamidine. N-hydroxypentamidine is further oxidized to the respective amide by reconstituted rabbit liver P-450 enzyme systems involving the oxidase and peroxidase activities of this enzyme. Formation of nitric oxide [(NO); endothelium-derived relaxing factor] during this oxidation is shown by the detection of the cytochrome P-420-Fe(II)-NO complex by visible difference spectroscopy. The possibility for the N-hydroxylation of pentamidine to the corresponding amidoximes and subsequent oxidative conversion to the respective amide derivatives is comparable with the physiological transformation of arginine to citrulline via N-hydroxyarginine with liberation of NO (endothelium-derived relaxing factor). The N-hydroxylated derivatives of pentamidine are easily retroreduced by microsomal fractions from rabbit liver. NADH is preferred to NADPH as cofactor for this reduction, and the reaction is strongly suppressed by the addition of N-methylylhydroxylamine. The N-hydroxylation of pentamidine and the retroreduction are also catalyzed by human liver microsomes.(ABSTRACT TRUNCATED AT 250 WORDS)

Log in using your username and password

Forgot your user name or password?

Pay Per Article - You may access this article (from the computer you are currently using) for 1 day for US$35.00

Regain Access - You can regain access to a recent Pay per Article purchase if your access period has not yet expired.

PreviousNext
Back to top

In this issue

Drug Metabolism and Disposition
Vol. 22, Issue 3
1 May 1994
  • Table of Contents
  • Table of Contents (PDF)
  • Index by author
  • Back Matter (PDF)
  • 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.
N-hydroxylation of the antiprotozoal drug pentamidine catalyzed by rabbit liver cytochrome P-450 2C3 or human liver microsomes, microsomal retroreduction, and further oxidative transformation of the formed amidoximes. Possible relationship to the biologi…
(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.
Citation Tools
Abstract

N-hydroxylation of the antiprotozoal drug pentamidine catalyzed by rabbit liver cytochrome P-450 2C3 or human liver microsomes, microsomal retroreduction, and further oxidative transformation of the formed amidoximes. Possible relationship to the biological oxidation of arginine to NG-hydroxyarginine, citrulline, and nitric oxide.

B Clement and F Jung
Drug Metabolism and Disposition May 1, 1994, 22 (3) 486-497;

Citation Manager Formats

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

Share
Abstract

N-hydroxylation of the antiprotozoal drug pentamidine catalyzed by rabbit liver cytochrome P-450 2C3 or human liver microsomes, microsomal retroreduction, and further oxidative transformation of the formed amidoximes. Possible relationship to the biological oxidation of arginine to NG-hydroxyarginine, citrulline, and nitric oxide.

B Clement and F Jung
Drug Metabolism and Disposition May 1, 1994, 22 (3) 486-497;
del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Jump to section

  • Article
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

Similar Articles

  • 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 © 2019 by the American Society for Pharmacology and Experimental Therapeutics