The Uridine diphosphate (UDP)-glycosyltransferases (UGTs) superfamily: the role in tumor cell metabolism

Front Oncol. 2023 Jan 19:12:1088458. doi: 10.3389/fonc.2022.1088458. eCollection 2022.

Abstract

UDP-glycosyltransferases (UGTs), important enzymes in biotransformation, control the levels and distribution of numerous endogenous signaling molecules and the metabolism of a wide range of endogenous and exogenous chemicals. The UGT superfamily in mammals consists of the UGT1, UGT2, UGT3, and UGT8 families. UGTs are rate-limiting enzymes in the glucuronate pathway, and in tumors, they are either overexpressed or underexpressed. Alterations in their metabolism can affect gluconeogenesis and lipid metabolism pathways, leading to alterations in tumor cell metabolism, which affect cancer development and prognosis. Glucuronidation is the most common mammalian conjugation pathway. Most of its reactions are mainly catalyzed by UGT1A, UGT2A and UGT2B. The body excretes UGT-bound small lipophilic molecules through the bile, urine, or feces. UGTs conjugate a variety of tiny lipophilic molecules to sugars, such as galactose, xylose, acetylglucosamine, glucuronic acid, and glucose, thereby inactivating and making water-soluble substrates, such as carcinogens, medicines, steroids, lipids, fatty acids, and bile acids. This review summarizes the roles of members of the four UGT enzyme families in tumor function, metabolism, and multiple regulatory mechanisms, and its Inhibitors and inducers. The function of UGTs in lipid metabolism, drug metabolism, and hormone metabolism in tumor cells are among the most important topics covered.

Keywords: UDP-glycosyltransferase; drug metabolism; hormone metabolism; lipid metabolism; tumor.

Publication types

  • Review

Grants and funding

This work was supported by National Natural Science Foundation for Young Scholars of China (Grant No.82202928 to PH), Jiangxi Provincial Department of Education Fund (GJJ211526 to YL) and the National College Students Innovation Entrepreneurship Training Plan Program of China (202210413009 to RZ and JL).