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Human udp-glucuronosyltransferases: isoform selectivity and kinetics of 4-methylumbelliferone and 1-naphthol glucuronidation, effects of organic solvents, and inhibition by diclofenac and probenecid.

Author: GaletinAleksandra, Gardner-StephenDione, GuoXiao-Hui, HoustonJ Brian, MackenziePeter I, MinersJohn O, UchaipichatVerawan

Comparative StudyResearch that compares multiple groups/interventions to determine differences/similarities in outcomes/characteristics.
Journal ArticleAn article published in an academic or professional journal that reports original research or scholarly analysis.
Research Support, Non-U.S. Gov'tResearch funding provided by government agencies outside the United States.

Overview

This study investigated the glucuronidation kinetics of two prototypic substrates, 4-methylumbelliferone (4MU) and 1-naphthol (1NP), by 11 human UDP-glucuronosyltransferases (UGTs). It found that all isoforms except UGT1A4 glucuronidated 4MU, while all but UGT 1A4, 2B15, and 2B17 metabolized 1NP. The kinetic models varied with the substrate and isoform. Diclofenac and probenecid inhibited all isoforms, while organic solvents generally had a minor effect on UGT activity.
Paper Details　
Original Abstract of the Article :
The glucuronidation kinetics of the prototypic substrates 4-methylumbelliferone (4MU) and 1-naphthol (1NP) by human UDP-glucuronosyltransferases (UGT) 1A1, 1A3, 1A4, 1A6, 1A7, 1A8, 1A9, 1A10, 2B7, 2B15, and 2B17 were investigated. Where activity was demonstrated, inhibitory effects of diclofenac, pr...See full text at original site
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引用元：
https://pubmed.ncbi.nlm.nih.gov/15039294

データ提供：米国国立医学図書館（NLM）

Human UDP-Glucuronosyltransferases: Exploring the Kinetics of Glucuronidation

This study delves into the [kinetics of glucuronidation], a key detoxification process in the body, by investigating the activity of various human UDP-glucuronosyltransferases (UGTs). Researchers examined the activity of different UGT isoforms in metabolizing two prototypic substrates, 4-methylumbelliferone (4MU) and 1-naphthol (1NP), analyzing the kinetic parameters and the effects of various inhibitors and solvents. This study provides valuable information for understanding the complex interactions of UGTs with different substrates and inhibitors.

A Desert of Enzyme Activity

Imagine the human body as a vast desert, with different enzymes working tirelessly to break down and eliminate harmful substances. UGTs are like specialized guides in this desert, facilitating the detoxification process. This study explores the intricate activity of these enzymes, revealing the complex relationships between different isoforms and substrates.

Navigating the Desert of Detoxification

This research provides a deeper understanding of the complex processes that govern detoxification in the human body. It highlights the importance of considering the interplay between different enzymes, substrates, and inhibitors. It's like navigating a desert landscape, where the path to detoxification requires a careful understanding of the terrain and the right tools for the journey.

Dr. Camel's Conclusion

This study provides a valuable roadmap for understanding the complex world of human UDP-glucuronosyltransferases. It highlights the intricate dance between different isoforms, substrates, and inhibitors, emphasizing the importance of personalized approaches for maximizing detoxification efficiency. It's like exploring a vast desert, where understanding the unique features of each pathway is crucial for navigating the terrain and reaching the destination of detoxification.

Date :
  1. Date Completed 2005-01-14
  2. Date Revised 2017-11-16
Further Info :

Pubmed ID

15039294

DOI: Digital Object Identifier

32/4/413

Related Literature

Article Analysis
・Effects of probenecid
SNS
PICO Info
in preparation
Languages

English

Positive IndicatorAn AI analysis index that serves as a benchmark for how positive the results of the study are. Note that it is a benchmark and requires careful interpretation and consideration of different perspectives.

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