The Role of UDP-Glycosyltransferases in Xenobiotic Metabolism

UDP-glycosyltransferases (UGTs) are enzymes from a complex superfamily of glycosyltransferases. UGTs catalyze glycosylation reactions, 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 many groups of organisms (mammals, arthropods, plants, etc.). UGTs are the main enzymes of phase II detoxification of xenobiotics of various origins (metals, natural compounds, drugs, industrial pollutants, pesticides, etc.). The human UGTs arouse interest due to their role in drug metabolism and involvement in the development of drug resistance in cancer cells. UDP-glycosyltransferases of invertebrates (especially insects) attract the attention of researchers because of their involvement in the development of pesticide resistance. However, the exact role of individual UGT families and subfamilies in xenobiotic biotransformation remains unclear, highlighting the importance of further study of these enzymes. This review aims to provide an understanding of the diversity of UDP-glycosyltransferases in vertebrates and invertebrates (arthropods) and some details of the interaction of these enzymes with xenobiotics. The section on general information briefly describes the structure and localization of the enzymes of the superfamily UGTs, the enzymatic reaction and the mechanism of catalysis using UDP-glucuronosyltransferase as an example. In addition, this review presents the data on the impact of different xenobiotics (industrial pollutants, metals, pesticides, drugs and natural compounds) on the enzymatic activity of UGTs and the level of UGT gene expressions in vertebrates and invertebrates (arthropods). The diversity of UGT enzymes and their substrates reflects the wide possibilities of the animal organism to protect themself from xenobiotics.