Unusual glucuronides
1Novartis Institutes for Biomedical Research, Inc., Metabolism and Pharmacokinetics, 250 Massachusetts Ave., Cambridge, MA 02139, USA. upendra.argikar@novartis.com
Summary
This review highlights unusual glucuronide conjugates formed by uridine diphosphoglucuronosyl transferases, focusing on those resulting from conjugation at uncommon sites and undergoing further metabolism. It clarifies diglucuronide classification for better understanding of these metabolites.
Area of Science:
- Biochemistry
- Drug Metabolism
- Pharmacokinetics
Background:
- Glucuronidation, catalyzed by uridine diphosphoglucuronosyl transferases, involves conjugating glucuronic acid to various chemical entities.
- Glucuronides are typically end products of metabolism, but can undergo further biotransformation.
- The nomenclature for diglucuronides is often inconsistent, hindering clear differentiation.
Purpose of the Study:
- To review and highlight unusual glucuronide conjugates.
- To clarify the classification of diglucuronide metabolites.
- To discuss structural and mechanistic aspects of unusual glucuronidation.
Main Methods:
- Literature review of unusual glucuronide conjugates.
- Analysis of diglucuronide classification and nomenclature.
- Discussion of structural and mechanistic aspects.
Main Results:
- Identified glucuronides formed at uncommon functional groups (e.g., carbon, selenium, N-carbamoylation).
- Highlighted glucuronides that undergo subsequent oxidative or conjugative biotransformations.
- Differentiated two categories of diglucuronides, addressing nomenclature inconsistencies.
Conclusions:
- Unusual glucuronide conjugates represent a significant area in drug metabolism and biotransformation.
- Clearer classification of diglucuronides is essential for accurate interpretation of metabolic pathways.
- Further research into the structural and mechanistic aspects of these unusual metabolites is warranted.
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