Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, Hradec Králové, Czech Republic.
Laboratory of Plant Biotechnologies, Institute of Experimental Botany, Czech Academy of Sciences, Praha, Czech Republic.
Drug Metab Rev. 2022 Aug;54(3):282-298. doi: 10.1080/03602532.2022.2083632. Epub 2022 Jun 12.
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.
尿苷二磷酸糖基转移酶（UGTs）是一类酶超家族，能够催化从活化核苷酸糖向受体分子转移糖基残基。除了各种内源性化合物外，许多外源化合物也是 UGTs 的底物。由于形成的糖苷通常比苷元活性/毒性更低，亲水性更强，UGTs 可有效保护生物体免受潜在有害的外源化合物的侵害。因此，增加 UGT 的表达和/或活性可以提高生物体的保护能力，并可能导致某些对外源化合物更具抵抗力的个体的发展。虽然 UGTs 在人类癌细胞对化疗的耐药性中的作用现在已经很清楚，但其他生物体和其他外源化合物的关注较少。本综述旨在通过介绍 UGTs 在各种生物体中外源化合物耐药性中的作用的复杂信息来填补这一知识空白。对现有信息的总结和评估表明，UGTs 不仅在人类中，而且在寄生虫、昆虫和植物等无数其他生物体中，在抵御外源化合物方面发挥着重要作用。此外，许多最近的研究清楚地表明 UGTs 参与了线虫对驱虫药、昆虫对杀虫剂、杂草对除草剂以及人类对各种药物（不仅是用于癌症治疗的药物，还包括治疗癫痫、精神障碍、高血压、高胆固醇血症和 HIV 感染的药物）的耐药性。然而，尽管 UGTs 在外源化合物耐药性方面在不同的生物体中的作用已经很明显，但仍有许多信息缺失，例如 UGT 调节的机制。
