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尿苷二磷酸(UDP)-糖基转移酶(UGTs)超家族:在肿瘤细胞代谢中的作用

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

作者信息

Liu Wenyu, Li Jing, Zhao Rui, Lu Yao, Huang Panpan

机构信息

School of Basic Medicine, Gannan Medical University, Ganzhou, Jiangxi, China.

出版信息

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.

摘要

尿苷二磷酸糖基转移酶(UGTs)是生物转化中的重要酶类,可控制多种内源性信号分子的水平和分布以及多种内源性和外源性化学物质的代谢。哺乳动物中的UGT超家族由UGT1、UGT2、UGT3和UGT8家族组成。UGTs是葡萄糖醛酸途径中的限速酶,在肿瘤中,它们要么过度表达,要么表达不足。其代谢改变可影响糖异生和脂质代谢途径,导致肿瘤细胞代谢改变,进而影响癌症的发展和预后。葡萄糖醛酸化是最常见的哺乳动物结合途径。其大多数反应主要由UGT1A、UGT2A和UGT2B催化。身体通过胆汁、尿液或粪便排泄与UGT结合的小亲脂性分子。UGTs将多种微小的亲脂性分子与糖类(如半乳糖、木糖、乙酰葡糖胺、葡糖醛酸和葡萄糖)结合,从而使致癌物、药物、类固醇、脂质、脂肪酸和胆汁酸等底物失活并使其具有水溶性。本综述总结了四个UGT酶家族成员在肿瘤功能、代谢和多种调控机制中的作用及其抑制剂和诱导剂。UGTs在肿瘤细胞脂质代谢、药物代谢和激素代谢中的功能是所涵盖的最重要主题之一。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/96e1/9892627/2f95e32c6414/fonc-12-1088458-g001.jpg

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