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Related Concept Videos

Phase II Reactions: Glucuronidation01:24

Phase II Reactions: Glucuronidation

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Glucuronidation, a pivotal phase II biotransformation process, involves the coupling of glucuronic acid to a drug or xenobiotic. Given its widespread occurrence and critical role in drug metabolism, it's considered the most crucial phase II reaction. It enhances the water solubility of substances, aiding their expulsion from the body. The driving force behind these reactions is a group of enzymes known as UDP-glucuronosyltransferases (UGTs). UGTs facilitate the transfer of a glucuronic acid...
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Phase II reactions are essential for the detoxification and elimination of drugs from the body. These reactions involve the conjugation of parent drugs or their phase I metabolites with endogenous molecules, resulting in more hydrophilic drug conjugates. The primary conjugation reactions in this phase are sulfation and glucuronidation. Both sulfation and glucuronidation typically produce biologically inactive metabolites. However, in some cases involving prodrugs, active metabolites may be...
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Androgen Glucuronidation in Mice: When, Where, and How.

Laurent Grosse1, Sarah Chouinard2, Sophie Pâquet1

  • 1Centre Hospitalié Universitaire de Québec Research Center, Laboratory of Molecular Pharmacology, Endocrinology and Nephrology Axis, Faculty of Pharmacy, Laval University, Québec, QC G1V 0A6, Canada.

Biology
|March 26, 2022
PubMed
Summary
This summary is machine-generated.

Murine UDP-glucuronosyltransferase UGT2B enzymes in the liver and kidney conjugate androgens like testosterone. Androgen levels influence UGT2B enzyme activity, revealing a self-regulatory pathway in mice.

Keywords:
UDP-glucuronosyltransferaseandrogen hormonesglucuronidationkinetic parametersliquid chromatography coupled with tandem mass spectrometrytissue distribution

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Area of Science:

  • Pharmacology
  • Biochemistry
  • Endocrinology

Background:

  • UDP-glucuronosyltransferase (UGT2B) enzymes are crucial for androgen hormone metabolism in humans.
  • The role of mouse UGT2B enzymes in androgen glucuronidation remains largely uncharacterized.

Purpose of the Study:

  • To investigate the capacity of murine tissues and UGT2B enzymes to glucuronidate androgens.
  • To identify the specific UGT2B enzymes and tissues involved in mouse androgen metabolism.

Main Methods:

  • Cloned and expressed seven murine Ugt2b enzymes in HEK293 cells.
  • Conducted in vitro glucuronidation assays using mouse tissue microsomes/homogenates and Ugt2b-HEK293 cells.
  • Investigated the effects of castration and dihydrotestosterone (DHT) injection on UGT2B expression and activity.

Main Results:

  • Male and female livers, along with male kidneys, are primary sites of androgen glucuronidation in mice.
  • Murine Ugt2b1 and Ugt2b5 enzymes in the liver efficiently glucuronidate dihydrotestosterone (DHT) and testosterone.
  • Ugt2b37 in the male kidney mediates androsterone and 3α-Diol conjugation.
  • Castration reduced hepatic Ugt2b1 and Ugt2b37 levels, with DHT partially restoring these changes.

Conclusions:

  • Murine UGT2B enzymes exhibit substrate- and tissue-specific androgen conjugation.
  • Androgens can modulate their own glucuronide conjugation in mice, indicating a feedback mechanism.