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The UDP-glucuronosyltransferases of the blood-brain barrier: their role in drug metabolism and detoxication
UDP-glucuronosyltransferases (UGTs) form a multigenic family of membrane-bound enzymes expressed in various tissues, including brain. They catalyze the formation of β-D-glucuronides from structurally unrelated substances (drugs, other xenobiotics, as well as endogenous compounds) by the linkage of g...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Frontiers Media S.A.
2014
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Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4211562/ https://www.ncbi.nlm.nih.gov/pubmed/25389387 http://dx.doi.org/10.3389/fncel.2014.00349 |
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author | Ouzzine, Mohamed Gulberti, Sandrine Ramalanjaona, Nick Magdalou, Jacques Fournel-Gigleux, Sylvie |
author_facet | Ouzzine, Mohamed Gulberti, Sandrine Ramalanjaona, Nick Magdalou, Jacques Fournel-Gigleux, Sylvie |
author_sort | Ouzzine, Mohamed |
collection | PubMed |
description | UDP-glucuronosyltransferases (UGTs) form a multigenic family of membrane-bound enzymes expressed in various tissues, including brain. They catalyze the formation of β-D-glucuronides from structurally unrelated substances (drugs, other xenobiotics, as well as endogenous compounds) by the linkage of glucuronic acid from the high energy donor, UDP-α-D-glucuronic acid. In brain, UGTs actively participate to the overall protection of the tissue against the intrusion of potentially harmful lipophilic substances that are metabolized as hydrophilic glucuronides. These metabolites are generally inactive, except for important pharmacologically glucuronides such as morphine-6-glucuronide. UGTs are mainly expressed in endothelial cells and astrocytes of the blood brain barrier (BBB). They are also associated to brain interfaces devoid of BBB, such as circumventricular organ, pineal gland, pituitary gland and neuro-olfactory tissues. Beside their key-role as a detoxication barrier, UGTs play a role in the steady-state of endogenous compounds, like steroids or dopamine (DA) that participate to the function of the brain. UGT isoforms of family 1A, 2A, 2B and 3A are expressed in brain tissues to various levels and are known to present distinct but overlapping substrate specificity. The importance of these enzyme species with regard to the formation of toxic, pharmacologically or physiologically relevant glucuronides in the brain will be discussed. |
format | Online Article Text |
id | pubmed-4211562 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-42115622014-11-11 The UDP-glucuronosyltransferases of the blood-brain barrier: their role in drug metabolism and detoxication Ouzzine, Mohamed Gulberti, Sandrine Ramalanjaona, Nick Magdalou, Jacques Fournel-Gigleux, Sylvie Front Cell Neurosci Neuroscience UDP-glucuronosyltransferases (UGTs) form a multigenic family of membrane-bound enzymes expressed in various tissues, including brain. They catalyze the formation of β-D-glucuronides from structurally unrelated substances (drugs, other xenobiotics, as well as endogenous compounds) by the linkage of glucuronic acid from the high energy donor, UDP-α-D-glucuronic acid. In brain, UGTs actively participate to the overall protection of the tissue against the intrusion of potentially harmful lipophilic substances that are metabolized as hydrophilic glucuronides. These metabolites are generally inactive, except for important pharmacologically glucuronides such as morphine-6-glucuronide. UGTs are mainly expressed in endothelial cells and astrocytes of the blood brain barrier (BBB). They are also associated to brain interfaces devoid of BBB, such as circumventricular organ, pineal gland, pituitary gland and neuro-olfactory tissues. Beside their key-role as a detoxication barrier, UGTs play a role in the steady-state of endogenous compounds, like steroids or dopamine (DA) that participate to the function of the brain. UGT isoforms of family 1A, 2A, 2B and 3A are expressed in brain tissues to various levels and are known to present distinct but overlapping substrate specificity. The importance of these enzyme species with regard to the formation of toxic, pharmacologically or physiologically relevant glucuronides in the brain will be discussed. Frontiers Media S.A. 2014-10-28 /pmc/articles/PMC4211562/ /pubmed/25389387 http://dx.doi.org/10.3389/fncel.2014.00349 Text en Copyright © 2014 Ouzzine, Gulberti, Ramalanjaona, Magdalou and Fournel-Gigleux. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution and reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms. |
spellingShingle | Neuroscience Ouzzine, Mohamed Gulberti, Sandrine Ramalanjaona, Nick Magdalou, Jacques Fournel-Gigleux, Sylvie The UDP-glucuronosyltransferases of the blood-brain barrier: their role in drug metabolism and detoxication |
title | The UDP-glucuronosyltransferases of the blood-brain barrier: their role in drug metabolism and detoxication |
title_full | The UDP-glucuronosyltransferases of the blood-brain barrier: their role in drug metabolism and detoxication |
title_fullStr | The UDP-glucuronosyltransferases of the blood-brain barrier: their role in drug metabolism and detoxication |
title_full_unstemmed | The UDP-glucuronosyltransferases of the blood-brain barrier: their role in drug metabolism and detoxication |
title_short | The UDP-glucuronosyltransferases of the blood-brain barrier: their role in drug metabolism and detoxication |
title_sort | udp-glucuronosyltransferases of the blood-brain barrier: their role in drug metabolism and detoxication |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4211562/ https://www.ncbi.nlm.nih.gov/pubmed/25389387 http://dx.doi.org/10.3389/fncel.2014.00349 |
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