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
  • Log out
  • 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
  • Log out
  • 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

Human and Escherichia coliβ-Glucuronidase Hydrolysis of Glucuronide Conjugates of Benzidine and 4-Aminobiphenyl, and their Hydroxy Metabolites

Terry V. Zenser, Vijaya M. Lakshmi and Bernard B. Davis
Drug Metabolism and Disposition September 1999, 27 (9) 1064-1067;
Terry V. Zenser
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Vijaya M. Lakshmi
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Bernard B. Davis
  • 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

Individuals exposed to carcinogenic aromatic amines excrete arylamine N- and O-glucuronide metabolites. This study assessed the susceptibility of selected glucuronides to hydrolysis by human and Escherichia coliβ-glucuronidase. N- or O-glucuronides were prepared with the following aglycones: benzidine,N-acetylbenzidine,N′-hydroxy-N-acetylbenzidine,N-hydroxy-N-acetylbenzidine,N-hydroxy-N,N′-diacetylbenzidine, 3-hydroxy-N,N′-diacetylbenzidine, 3-hydroxy-benzidine, 4-aminobiphenyl, N-hydroxy-4-aminobiphenyl, andN-hydroxy-N-acetyl-4-aminobiphenyl. The3H- and 14C-labeled glucuronides were prepared with human or rat liver microsomes using UDP-glucuronic acid as cosubstrate. Each of the 10 glucuronides (6–12 μM) was incubated at pH 5.5 or 7.0 with either human recombinant (pure) or E. coli (commercial preparation) β-glucuronidase for 30 min at 37°C. Hydrolysis was measured by HPLC. Reaction conditions were optimized, using the O-glucuronide ofN-hydroxy-N,N′-diacetylbenzidine. Both enzymes preferentially hydrolyzed O-glucuronides overN-glucuronides and distinguished between structural isomers. With E. coli β-glucuronidase at pH 7.0, selectivity was demonstrated by the complete hydrolysis ofN-hydroxy-N-acetyl-4-aminobiphenylO-glucuronide in the presence ofN-acetylbenzidine N-glucuronide, which was not hydrolyzed. Metabolism by both enzymes was completely inhibited by the specific β-glucuronidase inhibitor saccharic acid-1,4-lactone (0.5 mM). The concentration of human β-glucuronidase necessary to achieve significant hydrolysis of glucuronides was substantially more than the amount of enzyme reported previously to be present in urine under either normal or pathological conditions. The bacterial enzyme may hydrolyze O-glucuronides, but notN-glucuronides, in urine at neutral pH. Thus, the nonenzymatic hydrolysis of N-glucuronides by acidic urine is likely a more important source of free amine than enzymatic hydrolysis.

Footnotes

  • Send reprint requests to: Terry V. Zenser, Ph.D., Veterans Administration Medical Center (11G-JB), St. Louis, MO 63125-4199. E-mail: zensertv{at}slu.edu

  • This work was supported by the Department of Veterans Affairs (T.V.Z., B.B.D.) and National Cancer Institute Grant CA72613 (T.V.Z.).

    • Received February 9, 1999.
    • Accepted April 29, 1999.
  • 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: 27 (9)
Drug Metabolism and Disposition
Vol. 27, Issue 9
1 Sep 1999
  • Table of Contents
  • About the Cover
  • Index by author
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.
Human and Escherichia coliβ-Glucuronidase Hydrolysis of Glucuronide Conjugates of Benzidine and 4-Aminobiphenyl, and their Hydroxy Metabolites
(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

Human and Escherichia coliβ-Glucuronidase Hydrolysis of Glucuronide Conjugates of Benzidine and 4-Aminobiphenyl, and their Hydroxy Metabolites

Terry V. Zenser, Vijaya M. Lakshmi and Bernard B. Davis
Drug Metabolism and Disposition September 1, 1999, 27 (9) 1064-1067;

Citation Manager Formats

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

Share
Research ArticleArticle

Human and Escherichia coliβ-Glucuronidase Hydrolysis of Glucuronide Conjugates of Benzidine and 4-Aminobiphenyl, and their Hydroxy Metabolites

Terry V. Zenser, Vijaya M. Lakshmi and Bernard B. Davis
Drug Metabolism and Disposition September 1, 1999, 27 (9) 1064-1067;
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
    • Materials and Methods
    • Results
    • Discussion
    • Acknowledgments
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • TMDD Affects PK of IL-10 Fc-fusion Proteins
  • Uptake as the RDS in Pevonedistat Hepatic Clearance
  • In vitro downregulation of OATP1B1 by retinoids
Show more Article

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 © 2022 by the American Society for Pharmacology and Experimental Therapeutics