The Role of UDP-Glycosyltransferases in Xenobiotic Metabolism

UDP-glycosyltransferases (UGTs) are enzymes from a complexsuperfamily of glycosyltransferases. UGTs catalyze glycosylationreactions, i.e. the covalent addition of sugar from a cofactor (UDP-glycoside)to the corresponding functional group of a lipophilic substrate.These enzymes play a crucial role in cellular homeostasis of manygroups of organisms (mammals, arthropods, plants, etc.). UGTs are themain enzymes of phase II detoxification of xenobiotics of variousorigins (metals, natural compounds, drugs, industrial pollutants,pesticides, etc.). The human UGTs arouse interest due to their rolein drug metabolism and involvement in the development of drug resistancein cancer cells. UDP-glycosyltransferases of invertebrates (especiallyinsects) attract the attention of researchers because of their involvementin the development of pesticide resistance. However, the exact roleof individual UGT families and subfamilies in xenobiotic biotransformationremains unclear, highlighting the importance of further study ofthese enzymes. This review aims to provide an understanding of thediversity of UDP-glycosyltransferases in vertebrates and invertebrates(arthropods) and some details of the interaction of these enzymeswith xenobiotics. The section on general information briefly describesthe structure and localization of the enzymes of the superfamilyUGTs, the enzymatic reaction and the mechanism of catalysis usingUDP-glucuronosyltransferase as an example. In addition, this reviewpresents the data on the impact of different xenobiotics (industrialpollutants, metals, pesticides, drugs and natural compounds) onthe enzymatic activity of UGTs and the level of UGT gene expressionsin vertebrates and invertebrates (arthropods). The diversity ofUGT enzymes and their substrates reflects the wide possibilitiesof the animal organism to protect themself from xenobiotics.