Jove
Visualize
Contact Us
JoVE
x logofacebook logolinkedin logoyoutube logo
ABOUT JoVE
OverviewLeadershipBlogJoVE Help Center
AUTHORS
Publishing ProcessEditorial BoardScope & PoliciesPeer ReviewFAQSubmit
LIBRARIANS
TestimonialsSubscriptionsAccessResourcesLibrary Advisory BoardFAQ
RESEARCH
JoVE JournalMethods CollectionsJoVE Encyclopedia of ExperimentsArchive
EDUCATION
JoVE CoreJoVE BusinessJoVE Science EducationJoVE Lab ManualFaculty Resource CenterFaculty Site
Terms & Conditions of Use
Privacy Policy
Policies

Related Experiment Videos

Structure and function of uridine diphosphate glucuronosyltransferases

R Meech1, P I Mackenzie

  • 1Department of Clinical Pharmacology, Flinders University of South Australia, Australia.

Clinical and Experimental Pharmacology & Physiology
|December 24, 1997
PubMed
Summary

Uridine diphosphate (UDP)-glucuronosyltransferases (UGT) detoxify compounds by adding glucuronic acid. UGT structure, localization to the endoplasmic reticulum, and substrate specificity are key to their function in detoxification and drug metabolism.

Related Concept Videos

You might also read

Related Articles

Articles linked to this work by shared authors, journal, and citation graph.

Sort by
Same author

Steroid UDP glucuronosyltransferases.

The Journal of steroid biochemistry and molecular biology·2012
Same author

Liver-enriched transcription factors and their role in regulating UDP glucuronosyltransferase gene expression.

Current drug metabolism·2008
Same author

Comparative homology modeling of human cytochrome P4501A1 (CYP1A1) and confirmation of residues involved in 7-ethoxyresorufin O-deethylation by site-directed mutagenesis and enzyme kinetic analysis.

Archives of biochemistry and biophysics·2007
Same author

The glucuronidation of Delta4-3-Keto C19- and C21-hydroxysteroids by human liver microsomal and recombinant UDP-glucuronosyltransferases (UGTs): 6alpha- and 21-hydroxyprogesterone are selective substrates for UGT2B7.

Drug metabolism and disposition: the biological fate of chemicals·2006
Same author

BARX2 and estrogen receptor-alpha (ESR1) coordinately regulate the production of alternatively spliced ESR1 isoforms and control breast cancer cell growth and invasion.

Oncogene·2006
Same author

Glucuronidation of bioflavonoids by human UGT1A10: structure-function relationships.

Xenobiotica; the fate of foreign compounds in biological systems·2005

Area of Science:

  • Biochemistry
  • Enzymology
  • Pharmacology

Background:

  • Uridine diphosphate (UDP)-glucuronosyltransferases (UGT) are critical enzymes for xenobiotic and endogenous compound detoxification.
  • UGTs catalyze the conjugation of glucuronic acid to lipophilic substrates, enhancing their excretion.
  • Deficiencies in UGT function lead to severe health issues, such as hyperbilirubinemia.

Purpose of the Study:

  • To elucidate the structural and functional characteristics of UDP-glucuronosyltransferases.
  • To understand the substrate specificity and catalytic mechanisms of UGT enzymes.
  • To investigate the cellular localization and membrane topology of UGTs.

Main Methods:

  • Bioinformatic analysis of UGT protein sequences to identify conserved domains.

Related Experiment Videos

  • Enzyme kinetics studies to determine substrate binding and catalytic efficiency.
  • Subcellular fractionation and immunolocalization techniques to determine UGT localization within the endoplasmic reticulum.

    • Main Results:

    • UGT proteins possess distinct amino-terminal (aglycone specificity) and carboxyl-terminal (UDPGA binding) domains.
    • The aglycone binding site exhibits flexibility, accommodating structurally diverse substrates.
    • UGTs are type I transmembrane proteins localized to the endoplasmic reticulum, with the catalytic site in the lumen.

    Conclusions:

    • The distinct domain organization of UGTs dictates their substrate specificity and catalytic activity.
    • Endoplasmic reticulum localization and membrane association are crucial for UGT function and latency.
    • Understanding UGT structure-function relationships is vital for predicting drug metabolism and toxicity.