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
Research ArticleArticle

AMINO ACID RESIDUE ILE211 IS ESSENTIAL FOR THE ENZYMATIC ACTIVITY OF HUMAN UDP-GLUCURONOSYLTRANSFERASE 1A10 (UGT1A10)

Isabelle Martineau, André Tchernof and Alain Bélanger
Drug Metabolism and Disposition April 2004, 32 (4) 455-459; DOI: https://doi.org/10.1124/dmd.32.4.455
Isabelle Martineau
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
André Tchernof
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Alain Bélanger
  • 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

Conjugation of exogenous and endogenous compounds by uridine diphosphoglucuronosyltransferases (UGTs) is a pathway catalyzing the transfer of a glucuronic acid molecule from UDP glucuronic acid to lipophilic aglycones, which become more polar and more easily excretable in the bile or urine. UGTs are divided into two major families, UGT1 and UGT2. The isoform UGT1A10, along with UGT1A7 and UGT1A8, is expressed exclusively in extrahepatic tissues, notably in the gastrointestinal tract. Here, we report the isolation of a mutant clone of the human UGT1A10, at position 211 of the protein, where a threonine residue replaces an isoleucine residue (allele Thr211). Because the isoleucine is conserved among many UGT1A isoforms, we proceeded to the analysis of the activity of the wild-type UGT1A10 (T211I) and compared it with that of the variant enzyme (I211T*). In vitro assays with microsomal extracts from stably expressing human embryonic kidney 293 (HEK293) cells showed that the mutant enzyme lost all detectable activity toward major substrates, which demonstrate that the residue isoleucine at position 211 is essential for UGT1A10 activity. Mutant UGT1A10 (I211T*) also lost all detectable activity toward mycophenolic acid. Genomic DNA from 103 unrelated individuals was sequenced for this mutation, and two heterozygous genotypes were detected for this mutation (frequency: 2 per 100 individuals). Because UGT1A10 appears to be expressed in all gastrointestinal tissues and is active toward a wide range of substrates, lack of activity of this isoform may have an impact on individual glucuronidation efficiency.

Footnotes

  • ↵1 Abbreviations used are: UGT, UDP-glucuronosyltransferase; UDPGA, uridine diphosphoglucuronic acid; HEK293, human embryonic kidney 293; PCR, polymerase chain reaction.

  • This work was supported by the Canadian Institutes of Health Research (A.B.).

    • Received July 7, 2003.
    • Accepted December 22, 2003.
  • 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: 32 (4)
Drug Metabolism and Disposition
Vol. 32, Issue 4
1 Apr 2004
  • 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.
AMINO ACID RESIDUE ILE211 IS ESSENTIAL FOR THE ENZYMATIC ACTIVITY OF HUMAN UDP-GLUCURONOSYLTRANSFERASE 1A10 (UGT1A10)
(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

AMINO ACID RESIDUE ILE211 IS ESSENTIAL FOR THE ENZYMATIC ACTIVITY OF HUMAN UDP-GLUCURONOSYLTRANSFERASE 1A10 (UGT1A10)

Isabelle Martineau, André Tchernof and Alain Bélanger
Drug Metabolism and Disposition April 1, 2004, 32 (4) 455-459; DOI: https://doi.org/10.1124/dmd.32.4.455

Citation Manager Formats

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

AMINO ACID RESIDUE ILE211 IS ESSENTIAL FOR THE ENZYMATIC ACTIVITY OF HUMAN UDP-GLUCURONOSYLTRANSFERASE 1A10 (UGT1A10)

Isabelle Martineau, André Tchernof and Alain Bélanger
Drug Metabolism and Disposition April 1, 2004, 32 (4) 455-459; DOI: https://doi.org/10.1124/dmd.32.4.455
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
    • Materials and Methods
    • Results
    • Discussion
    • Footnotes
    • References
  • Figures & Data
  • Info & Metrics
  • eLetters
  • PDF

Related Articles

Cited By...

More in this TOC Section

  • High-Throughput Characterization of SLCO1B1 VUS
  • Clearance Pathways: Fevipiprant with Probenecid Perpetrator
  • Retroconversion of PQ and Its N-Oxide Metabolites
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 © 2021 by the American Society for Pharmacology and Experimental Therapeutics