The UDP |
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The UDP
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UDP-glycosyltransferases (UGTs) catalyze the covalent addition of sugars to a broad range of lipophilic molecules. This biotransformation plays a critical role in elimination of a broad range of exogenous chemicals and by-products of endogenous metabolism, and also controls the levels and distribution of many endogenous signaling molecules. In mammals, the superfamily comprises four families: UGT1, UGT2, UGT3, and UGT8. UGT1 and UGT2 enzymes have important roles in pharmacology and toxicology including contributing to interindividual differences in drug disposition as well as to cancer risk. These UGTs are highly expressed in organs of detoxification (e.g., liver, kidney, intestine) and can be induced by pathways that sense demand for detoxification and for modulation of endobiotic signaling molecules. The functions of the UGT3 and UGT8 family enzymes have only been characterized relatively recently; these enzymes show different UDP-sugar preferences to that of UGT1 and UGT2 enzymes, and to date, their contributions to drug metabolism appear to be relatively minor. This review summarizes and provides critical analysis of the current state of research into all four families of UGT enzymes. Key areas discussed include the roles of UGTs in drug metabolism, cancer risk, and regulation of signaling, as well as the transcriptional and posttranscriptional control of UGT expression and function. The latter part of this review provides an in-depth analysis of the known and predicted functions of UGT3 and UGT8 enzymes, focused on their likely roles in modulation of levels of endogenous signaling pathways.
中文翻译：
UDP-糖基转移酶（UGT）催化糖与多种亲脂性分子的共价添加。这种生物转化在消除广泛的内源性化学物质和内源性代谢副产物中起着至关重要的作用，并且还控制着许多内源性信号分子的水平和分布。在哺乳动物中，超家族包括四个家族：UGT1，UGT2，UGT3和UGT8。UGT1和UGT2酶在药理和毒理学中具有重要作用，包括导致个体间药物配置差异以及癌症风险。这些UGT在解毒器官（例如，肝，肾，肠）中高度表达，并且可以通过感知对解毒和调节内源性信号分子的需求的途径来诱导。UGT3和UGT8家族酶的功能只是最近才被鉴定出来。这些酶显示出与UGT1和UGT2酶不同的UDP糖偏爱，迄今为止，它们对药物代谢的贡献似乎相对较小。这篇综述总结并提供了对UGT酶所有四个家族的当前研究状态的批判性分析。讨论的关键领域包括UGT在药物代谢中的作用，癌症风险和信号传导的调控，以及UGT表达和功能的转录和转录后控制。本文的后一部分将对UGT3和UGT8酶的已知功能和预测功能进行深入分析，重点是它们在调节内源性信号通路中的可能作用。 |
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