TY - JOUR
T1 - The UDP-glucuronosyltransferases: Their role in drug metabolism and detoxification
AU - Rowland, Andrew
AU - Miners, John
AU - Mackenzie, Peter
PY - 2013/6
Y1 - 2013/6
N2 - Human UDP-glucuronosyltransferase (UGT) exists as a superfamily of 22 proteins, which are divided into 5 families and 6 subfamilies on the basis of sequence identity. Members of the UGT1A and 2B subfamilies play a key role in terminating the biological actions and enhancing the renal elimination of non-polar (lipophilic) drugs from all therapeutic classes. These enzymes primarily catalyse the covalent linkage of glucuronic acid, derived from the cofactor UDP-glucuronic acid, to a substrate with a suitable acceptor functional group. This process is referred to as glucuronidation. While the liver is the major detoxification organ, and as such contains the greatest abundance and diversity of UGTs, these enzymes also exhibit significant, but variable extra-hepatic expression. This review discusses recent advances in the understanding of the functional roles of UGT, their regulation and tissue expression, and clinical significant factors (ontogeny, interactions and polymorphisms) that affect glucuronidation activity in humans.
AB - Human UDP-glucuronosyltransferase (UGT) exists as a superfamily of 22 proteins, which are divided into 5 families and 6 subfamilies on the basis of sequence identity. Members of the UGT1A and 2B subfamilies play a key role in terminating the biological actions and enhancing the renal elimination of non-polar (lipophilic) drugs from all therapeutic classes. These enzymes primarily catalyse the covalent linkage of glucuronic acid, derived from the cofactor UDP-glucuronic acid, to a substrate with a suitable acceptor functional group. This process is referred to as glucuronidation. While the liver is the major detoxification organ, and as such contains the greatest abundance and diversity of UGTs, these enzymes also exhibit significant, but variable extra-hepatic expression. This review discusses recent advances in the understanding of the functional roles of UGT, their regulation and tissue expression, and clinical significant factors (ontogeny, interactions and polymorphisms) that affect glucuronidation activity in humans.
KW - Detoxification
KW - Drug metabolism
KW - Elimination
KW - Glucuronidation
KW - UDP-glucuronosyltransferase
UR - http://www.scopus.com/inward/record.url?scp=84875924213&partnerID=8YFLogxK
U2 - 10.1016/j.biocel.2013.02.019
DO - 10.1016/j.biocel.2013.02.019
M3 - Review article
SN - 1357-2725
VL - 45
SP - 1121
EP - 1132
JO - International Journal of Biochemistry and Cell Biology
JF - International Journal of Biochemistry and Cell Biology
IS - 6
ER -