Abstract
UDP-glucuronosyltransferases (UGTs) belong to the Phase II drug metabolizing enzymes. UGTs mediate the transfer of glucuronic acid, from UDP glucuronic acid to predominantly hydrophobic xeno- and endobiotic chemicals, thus facilitating their detoxification and excretion. Deficiency in the expression and/or activity of UGTs may lead to genetic and acquired diseases such as Crigler-Najjar syndrome and jaundice. UGT genes are classified into UGT1A and UGT2B subfamily, and each subfamily and each isoform shows tissue-specific distribution pattern. The underlying mechanisms for this tissue specificity are not fully understood. Emerging evidence have demonstrated that nuclear receptors (NR), such as pregnane X receptor (PXR), constitutive androstane receptor (CAR), peroxisome proliferator-activated receptor (PPAR), can regulate UGTs and this NR-mediated regulation may contribute to the tissue-specific expression pattern of UGTs. The regulations are believed to be both receptor- and UGT isoform-specific. In addition, UGTs are also subject to the regulation by aryl hydrocarbon receptor (AhR) and other tissue-specific transcription factors. Based on their capacity to catalyze the glucuronidation of xenobiotics and endobiotics, UGTs play an important role in hormonal homeostasis, energy metabolism, bilirubin clearance, and xenobiotic detoxification. Therefore, elucidating UGT regulation by nuclear receptors has broader significance in understanding UGTs function in various physiological and pathophysiological conditions.
Keywords: nuclear receptors, transcriptional factor, gene regulation, xenobiotic receptor, udp-glucuronosyltransferase, transgenic mice, bilirubin homeostasis, hormonal homeostasis
Current Drug Metabolism
Title: Xenobiotic Nuclear Receptor-Mediated Regulation of UDP-Glucuronosyltransferases
Volume: 6 Issue: 4
Author(s): J. Zhou, J. Zhang and W. Xie
Affiliation:
Keywords: nuclear receptors, transcriptional factor, gene regulation, xenobiotic receptor, udp-glucuronosyltransferase, transgenic mice, bilirubin homeostasis, hormonal homeostasis
Abstract: UDP-glucuronosyltransferases (UGTs) belong to the Phase II drug metabolizing enzymes. UGTs mediate the transfer of glucuronic acid, from UDP glucuronic acid to predominantly hydrophobic xeno- and endobiotic chemicals, thus facilitating their detoxification and excretion. Deficiency in the expression and/or activity of UGTs may lead to genetic and acquired diseases such as Crigler-Najjar syndrome and jaundice. UGT genes are classified into UGT1A and UGT2B subfamily, and each subfamily and each isoform shows tissue-specific distribution pattern. The underlying mechanisms for this tissue specificity are not fully understood. Emerging evidence have demonstrated that nuclear receptors (NR), such as pregnane X receptor (PXR), constitutive androstane receptor (CAR), peroxisome proliferator-activated receptor (PPAR), can regulate UGTs and this NR-mediated regulation may contribute to the tissue-specific expression pattern of UGTs. The regulations are believed to be both receptor- and UGT isoform-specific. In addition, UGTs are also subject to the regulation by aryl hydrocarbon receptor (AhR) and other tissue-specific transcription factors. Based on their capacity to catalyze the glucuronidation of xenobiotics and endobiotics, UGTs play an important role in hormonal homeostasis, energy metabolism, bilirubin clearance, and xenobiotic detoxification. Therefore, elucidating UGT regulation by nuclear receptors has broader significance in understanding UGTs function in various physiological and pathophysiological conditions.
Export Options
About this article
Cite this article as:
Zhou J., Zhang J. and Xie W., Xenobiotic Nuclear Receptor-Mediated Regulation of UDP-Glucuronosyltransferases, Current Drug Metabolism 2005; 6 (4) . https://dx.doi.org/10.2174/1389200054633853
DOI https://dx.doi.org/10.2174/1389200054633853 |
Print ISSN 1389-2002 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5453 |
Call for Papers in Thematic Issues
Impact of brain tissue binding and plasma protein binding of drugs in DMPK
The impression of brain tissue binding (BTB) or plasma protein binding (PPB) in Drug Metabolism and Pharmacokinetics is critical to understanding the distribution, efficacy, and potential toxicity of drugs that target the central nervous system (CNS). BTB and high PPB influence the distribution of drugs in the body and their ...read more
Interaction between drugs and endocrine diseases
The introduction of highly active antiretroviral therapy accelerated studies and our understanding on the interaction between pharmacological therapies and endocrine diseases. Drugs can precipitate endocrine via different mechanisms, including direct alteration of hormone production and secretion, dysregulation of hormonal axis, effects on hormonal transport, receptor-binding, and cellular signalling. Common drug-induced ...read more
Metabolism-Mediated Xenobiotic Toxicity
Considering the potent modulation of biotransformation enzyme expression and activities by various therapeutic drugs and environmental chemicals, and the commonly combined exposure of humans to both drugs and the ever increasing environmental pollutants simultaneously, knowledge about the combined toxic effects by modulating biotransformation enzymes, such as P450s, UDP- glucuronosyltransferases, and ...read more
Safety evaluation of vaccine combination
Vaccine combination safety evaluation is a critical field within immunology and public health that focuses on assessing the safety and efficacy of combining different vaccines to maximize protection against various diseases while minimizing potential adverse effects. This process is significant because it ensures that vaccines can be administered together without ...read more

- Author Guidelines
- Bentham Author Support Services (BASS)
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
Breaking the Barrier of Cancer Through Liposome Loaded with Phytochemicals
Current Drug Delivery Localised Delivery of Therapeutic Agents to CNS Malignancies: Old and New Approaches
Current Pharmaceutical Biotechnology Hypoxia and Oxidative Stress in the Pathogenesis of Gynecological Cancers and in Therapeutical Options
Current Cancer Therapy Reviews Gastrointestinal Immune System and Brain Dialogue Implicated in Neuroinflammatory and Neurodegenerative Diseases
Current Molecular Medicine Avian Cytokines - An Overview
Current Pharmaceutical Design Recent Progress in the Development of Selective TRPV1 Antagonists for Pain
Current Topics in Medicinal Chemistry The Transcription Factor ETS-1: Its Role in Tumour Development and Strategies for its Inhibition
Mini-Reviews in Medicinal Chemistry The Potential of Natural Products as Effective Treatments for Allergic Inflammation: Implications for Allergic Rhinitis
Current Topics in Medicinal Chemistry An Overview of Privileged Scaffold: Quinolines and Isoquinolines in Medicinal Chemistry as Anticancer Agents
Current Topics in Medicinal Chemistry Non Pregnant Human Uterus as Source of Mesenchymal Stem Cells
Current Stem Cell Research & Therapy Nanotechnology Advances in Brain Tumors: The State of the Art
Recent Patents on Anti-Cancer Drug Discovery Natural Endoperoxides as Drug Lead Compounds
Current Medicinal Chemistry Editorial (Thematic issue: Discovering New Anticancer Activities from Old Drugs)
Current Medicinal Chemistry Regulation of Ion Channels, Cellular Carriers and Na(+)/K(+)/ATPase by Janus Kinase 3
Current Medicinal Chemistry Trends and Prospects of Plant Proteases in Therapeutics
Current Medicinal Chemistry The Ubiquitin-Proteasome System as a Prospective Molecular Target for Cancer Treatment and Prevention
Current Protein & Peptide Science Anti Tumor Necrosis Factor Alpha (TNFα) Therapy in Ankylosing Spondylitis - Asian Perspective
Current Rheumatology Reviews The Role of Snail in EMT and Tumorigenesis
Current Cancer Drug Targets Epidermal Growth Factor Receptor (EGFR) Tyrosine Kinase Inhibitors from the Natural Origin: A Recent Perspective
Anti-Cancer Agents in Medicinal Chemistry Polyphenol Supplementation as a Complementary Medicinal Approach to Treating Inflammatory Bowel Disease
Current Medicinal Chemistry