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Pharmaceutics 2017, 9(3), 32; https://doi.org/10.3390/pharmaceutics9030032

Revisiting the Latency of Uridine Diphosphate-Glucuronosyltransferases (UGTs)—How Does the Endoplasmic Reticulum Membrane Influence Their Function?

Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC V6T 1Z3, Canada
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Received: 7 August 2017 / Revised: 26 August 2017 / Accepted: 28 August 2017 / Published: 30 August 2017
(This article belongs to the Special Issue Pharmacokinetics and Drug Metabolism in Canada: The Current Landscape)
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Abstract

Uridine diphosphate-glucuronosyltransferases (UGTs) are phase 2 conjugation enzymes mainly located in the endoplasmic reticulum (ER) of the liver and many other tissues, and can be recovered in artificial ER membrane preparations (microsomes). They catalyze glucuronidation reactions in various aglycone substrates, contributing significantly to the body’s chemical defense mechanism. There has been controversy over the last 50 years in the UGT field with respect to the explanation for the phenomenon of latency: full UGT activity revealed by chemical or physical disruption of the microsomal membrane. Because latency can lead to inaccurate measurements of UGT activity in vitro, and subsequent underprediction of drug clearance in vivo, it is important to understand the mechanisms behind this phenomenon. Three major hypotheses have been advanced to explain UGT latency: compartmentation, conformation, and adenine nucleotide inhibition. In this review, we discuss the evidence behind each hypothesis in depth, and suggest some additional studies that may reveal more information on this intriguing phenomenon. View Full-Text
Keywords: UDP-glucuronosyltransferase; latency; microsomes; glucuronidation; regulation UDP-glucuronosyltransferase; latency; microsomes; glucuronidation; regulation
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Liu, Y.; Coughtrie, M.W.H. Revisiting the Latency of Uridine Diphosphate-Glucuronosyltransferases (UGTs)—How Does the Endoplasmic Reticulum Membrane Influence Their Function? Pharmaceutics 2017, 9, 32.

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