Revisiting the Latency of Uridine Diphosphate-Glucuronosyltransferases (UGTs)—How Does the Endoplasmic Reticulum Membrane Influence Their Function?
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 aglyc...
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doaj-8d99ec3b95b342048cdc366c14790ce12020-11-25T02:28:58ZengMDPI AGPharmaceutics1999-49232017-08-01933210.3390/pharmaceutics9030032pharmaceutics9030032Revisiting the Latency of Uridine Diphosphate-Glucuronosyltransferases (UGTs)—How Does the Endoplasmic Reticulum Membrane Influence Their Function?Yuejian Liu0Michael W. H. Coughtrie1Faculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC V6T 1Z3, CanadaFaculty of Pharmaceutical Sciences, The University of British Columbia, Vancouver, BC V6T 1Z3, CanadaUridine 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.https://www.mdpi.com/1999-4923/9/3/32UDP-glucuronosyltransferaselatencymicrosomesglucuronidationregulation |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Yuejian Liu Michael W. H. Coughtrie |
spellingShingle |
Yuejian Liu Michael W. H. Coughtrie Revisiting the Latency of Uridine Diphosphate-Glucuronosyltransferases (UGTs)—How Does the Endoplasmic Reticulum Membrane Influence Their Function? Pharmaceutics UDP-glucuronosyltransferase latency microsomes glucuronidation regulation |
author_facet |
Yuejian Liu Michael W. H. Coughtrie |
author_sort |
Yuejian Liu |
title |
Revisiting the Latency of Uridine Diphosphate-Glucuronosyltransferases (UGTs)—How Does the Endoplasmic Reticulum Membrane Influence Their Function? |
title_short |
Revisiting the Latency of Uridine Diphosphate-Glucuronosyltransferases (UGTs)—How Does the Endoplasmic Reticulum Membrane Influence Their Function? |
title_full |
Revisiting the Latency of Uridine Diphosphate-Glucuronosyltransferases (UGTs)—How Does the Endoplasmic Reticulum Membrane Influence Their Function? |
title_fullStr |
Revisiting the Latency of Uridine Diphosphate-Glucuronosyltransferases (UGTs)—How Does the Endoplasmic Reticulum Membrane Influence Their Function? |
title_full_unstemmed |
Revisiting the Latency of Uridine Diphosphate-Glucuronosyltransferases (UGTs)—How Does the Endoplasmic Reticulum Membrane Influence Their Function? |
title_sort |
revisiting the latency of uridine diphosphate-glucuronosyltransferases (ugts)—how does the endoplasmic reticulum membrane influence their function? |
publisher |
MDPI AG |
series |
Pharmaceutics |
issn |
1999-4923 |
publishDate |
2017-08-01 |
description |
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. |
topic |
UDP-glucuronosyltransferase latency microsomes glucuronidation regulation |
url |
https://www.mdpi.com/1999-4923/9/3/32 |
work_keys_str_mv |
AT yuejianliu revisitingthelatencyofuridinediphosphateglucuronosyltransferasesugtshowdoestheendoplasmicreticulummembraneinfluencetheirfunction AT michaelwhcoughtrie revisitingthelatencyofuridinediphosphateglucuronosyltransferasesugtshowdoestheendoplasmicreticulummembraneinfluencetheirfunction |
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