The role of UDP-glycosyltransferases in xenobioticresistance

Abstract

Uridine diphosphate sugar-utilizing glycosyltransferases (UGTs) are an enzyme superfamily that catalyzes glycosyl residues transfer from activated nucleotide sugars to acceptor molecules. In addition to various endogenous compounds, numerous xenobiotics are substrates of UGTs. As the glycosides formed are generally less active/toxic and more hydrophilic than aglycones, UGTs effectively protect organisms from potentially harmful xenobiotics. Therefore, increased UGT expression and/or activity improve the protection of the organism and may contribute to the development of individuals that become more resistant to certain xenobiotics. While the function of UGTs in the resistance of human cancer cells to chemotherapy is now well known, other organisms and other xenobiotics have attracted much less attention. This review was designed to fill this knowledge gap by presenting complex information about the role of UGTs in xenobiotic-resistance in various organisms. This summarization and evaluation of the available information reveals that UGTs play an important role in defense against xenobiotics not only in humans, but in countless other organisms such as parasites, insects, and plants. Moreover, many recent studies clearly show the participation of UGTs in the resistance of nematodes to anthelmintics, insects to insecticides, weeds to herbicides as well as humans to various drugs (not only those used in cancer therapy but also in the treatment of epilepsy, psychiatric disorders, hypertension, hypercholesterolemia, and HIV infection). Nevertheless, although the contribution of UGTs to xenobiotic resistance in diverse organisms has become obvious, many pieces of information remain missing, for example with regard to the mechanisms of UGT regulation.

Keywords:

• UGT
• xenobiotic glycosylation
• drug-resistance
• herbicide-resistance
• insecticide-resistance
• anthelmintic resistance

Acknowledgments

We would like to thank Daniel Sampey, MFA for the English revision.

Disclosure statement

Authors disclose financial or non-financial interests that are directly or indirectly related to this work.

Additional information

Funding

This work was supported by Charles University in Prague, the project UNCE/18/SCI/012, and the project “Grant Schemes at CU” reg. no. CZ.02.2.69/0.0/0.0/19_073/0016935.