Skip to main content
Advertisement

Main menu

  • Home
  • Articles
    • Current Issue
    • Fast Forward
    • Latest Articles
    • 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
  • 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
    • 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
  • Visit dmd on Facebook
  • Follow dmd on Twitter
  • Follow ASPET on LinkedIn
Rapid CommunicationShort Communication

The Human UDP-Glucuronosyltransferase UGT2A1 and UGT2A2 Enzymes Are Highly Active in Bile Acid Glucuronidation

Martin Perreault, Louis Gauthier-Landry, Jocelyn Trottier, Mélanie Verreault, Patrick Caron, Moshe Finel and Olivier Barbier
Drug Metabolism and Disposition September 2013, 41 (9) 1616-1620; DOI: https://doi.org/10.1124/dmd.113.052613
Martin Perreault
Laboratory of Molecular Pharmacology, CHU-Québec Research Centre, Faculty of Pharmacy, Laval University, Québec City, Québec, Canada (M.P., L.G.-L., J.T., M.V., P.C., O.B.); and Centre of Drug Research and Division of Pharmaceutical Chemistry, University of Helsinki, Finland (M.F.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Louis Gauthier-Landry
Laboratory of Molecular Pharmacology, CHU-Québec Research Centre, Faculty of Pharmacy, Laval University, Québec City, Québec, Canada (M.P., L.G.-L., J.T., M.V., P.C., O.B.); and Centre of Drug Research and Division of Pharmaceutical Chemistry, University of Helsinki, Finland (M.F.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Jocelyn Trottier
Laboratory of Molecular Pharmacology, CHU-Québec Research Centre, Faculty of Pharmacy, Laval University, Québec City, Québec, Canada (M.P., L.G.-L., J.T., M.V., P.C., O.B.); and Centre of Drug Research and Division of Pharmaceutical Chemistry, University of Helsinki, Finland (M.F.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Mélanie Verreault
Laboratory of Molecular Pharmacology, CHU-Québec Research Centre, Faculty of Pharmacy, Laval University, Québec City, Québec, Canada (M.P., L.G.-L., J.T., M.V., P.C., O.B.); and Centre of Drug Research and Division of Pharmaceutical Chemistry, University of Helsinki, Finland (M.F.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Patrick Caron
Laboratory of Molecular Pharmacology, CHU-Québec Research Centre, Faculty of Pharmacy, Laval University, Québec City, Québec, Canada (M.P., L.G.-L., J.T., M.V., P.C., O.B.); and Centre of Drug Research and Division of Pharmaceutical Chemistry, University of Helsinki, Finland (M.F.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Moshe Finel
Laboratory of Molecular Pharmacology, CHU-Québec Research Centre, Faculty of Pharmacy, Laval University, Québec City, Québec, Canada (M.P., L.G.-L., J.T., M.V., P.C., O.B.); and Centre of Drug Research and Division of Pharmaceutical Chemistry, University of Helsinki, Finland (M.F.)
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Olivier Barbier
Laboratory of Molecular Pharmacology, CHU-Québec Research Centre, Faculty of Pharmacy, Laval University, Québec City, Québec, Canada (M.P., L.G.-L., J.T., M.V., P.C., O.B.); and Centre of Drug Research and Division of Pharmaceutical Chemistry, University of Helsinki, Finland (M.F.)
  • 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

Bile acids (BA) are essential modulators of lipid, glucose, and cholesterol homeostasis, but they exert cytotoxic effects in the cholestatic liver. Glucuronidation, catalyzed by the UDP-glucuronosyltransferase (UGT) enzymes is a pharmacologically relevant BA detoxification process. The present study characterized the BA-conjugating activity of the little-studied human UGTs of subfamily 2A: UGT2A1, 2A2, and 2A3. Recombinant UGT2As, expressed in baculovirus-infected insect cells, were assayed for the glucuronidation of six major bile acids: chenodeoxycholic acid (CDCA), cholic acid (CA), lithocholic acid (LCA), deoxycholic acid (DCA), hyocholic acid (HCA) and hyodeoxycholic acid (HDCA). UGT2A3 exhibited detectable but very low activity with all the tested BA substrates. UGT2A1 was highly efficient in forming LCA-3 and LCA-24G, CDCA-24, DCA-24, HCA-24, and HDCA-24G, whereas UGT2A2 was the most active enzyme for CA-24G and CDCA-24G formation and also was able to generate HDCA-6G, HDCA-24G, LCA-24G, and HCA-24G. The Km values of UGT2A1 varied between 102.2 ± 14.3 µM and 2.4 ± 1.2 mM. With the exception of CA-24G, a low affinity substrate for UGT2A2, all the Km values for UGT2A2 were in the 100 to 400 µM range. We demonstrate the high reactivity of the human UGT2A1 and UGT2A2 for bile acid glucuronidation. The physiologic importance of these reactions to BA disposition remains, however, to be clarified in vivo.

Footnotes

    • Received April 29, 2013.
    • Accepted June 11, 2013.
  • This study was supported by grants from the Canadian Institute of Health Research [Grants MOP-84338, MSH95330]; the Canadian Liver Foundation; the Natural Sciences and Engineering Research Council of Canada; the Canadian Foundation for Innovation [Grant 10469]; the “Fonds pour la Recherche en Santé du Québec”; the Academy of Finland [Grant 1260010]; and the Sigrid Juselius Foundation.

  • dx.doi.org/10.1124/dmd.113.052613.

  • 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 (9)
Drug Metabolism and Disposition
Vol. 41, Issue 9
1 Sep 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.
The Human UDP-Glucuronosyltransferase UGT2A1 and UGT2A2 Enzymes Are Highly Active in Bile Acid Glucuronidation
(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
Rapid CommunicationShort Communication

UGT2A1 and UGT2A2 Glucuronidate Bile Acids

Martin Perreault, Louis Gauthier-Landry, Jocelyn Trottier, Mélanie Verreault, Patrick Caron, Moshe Finel and Olivier Barbier
Drug Metabolism and Disposition September 1, 2013, 41 (9) 1616-1620; DOI: https://doi.org/10.1124/dmd.113.052613

Citation Manager Formats

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

UGT2A1 and UGT2A2 Glucuronidate Bile Acids

Martin Perreault, Louis Gauthier-Landry, Jocelyn Trottier, Mélanie Verreault, Patrick Caron, Moshe Finel and Olivier Barbier
Drug Metabolism and Disposition September 1, 2013, 41 (9) 1616-1620; DOI: https://doi.org/10.1124/dmd.113.052613
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
    • Abstract
    • Introduction
    • Materials and Methods
    • Results and Discussion
    • Conclusion
    • Acknowledgments
    • Authorship Contributions
    • Footnotes
    • Abbreviations
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • Preincubation Effects on Inhibition of OCT1 by CsA
  • Carbamazepine Metabolite and Hypersensitivity Reactions
  • SULT4A1 Preserves Mitochondrial Function
Show more Short Communications

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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics