负责岩白菜素体外葡萄糖醛酸化的人尿苷二磷酸葡萄糖醛酸基转移酶的鉴定与表征
Identification and characterization of human UDP-glucuronosyltransferases responsible for the in vitro glucuronidation of bergenin.
作者信息
Song Haojing, Wang Jin, Zhang Rui, Liu Xiaoyan, Yuan Guiyan, Wei Chunmin, Wang Benjie, Guo Ruichen
机构信息
Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People's Republic of China; Department of Pharmacology, Shandong University School of Medicine, Jinan, Shandong, 250012, People's Republic of China.
出版信息
Biomed Chromatogr. 2014 Mar;28(3):348-53. doi: 10.1002/bmc.3027. Epub 2013 Sep 2.
Glucuronidation plays critical role in the elimination of bergenin; however the metabolic mechanism of UDP-glucuronosyltransferases (UGTs) in the process remains to be investigated. In this study, the kinetics of bergenin glucuronidation by pooled human liver microsomes (HLMs) and 12 recombinat UGT isozymes were investigated. The glucuronidation of bergenin can be shown in HLMs with a Km value of 231.62 ± 14.08 µm and a Vmax value of 2.17 ± 0.21 nmol/min/(mg protein). Among the 12 human UGTs investigated, UGT1A1 was identified as the major isoform catalyzing the glucuronidation of bergenin [Km value of 200.37 ± 26.73 µm and Vmax value of 1.88 ± 0.26 nmol/min/(mg protein)]. The bergenin glucuronosyltransferase activities in HLMs and UGT1A1 were inhibited by phenylbutazone, estradiol and bilirubin. The results demonstrate that bergenin glucuronidation in HLMs is specifically catalyzed by UGT1A1.
葡萄糖醛酸化在岩白菜素的消除过程中起着关键作用；然而，尿苷二磷酸葡萄糖醛酸基转移酶（UGTs）在此过程中的代谢机制仍有待研究。在本研究中，研究了人肝微粒体（HLMs）池和12种重组UGT同工酶对岩白菜素葡萄糖醛酸化的动力学。岩白菜素在HLMs中的葡萄糖醛酸化表现为Km值为231.62±14.08µm，Vmax值为2.17±0.21nmol/min/（mg蛋白质）。在所研究的12种人UGT中，UGT1A1被确定为催化岩白菜素葡萄糖醛酸化的主要同工酶[Km值为200.37±26.73µm，Vmax值为1.88±0.26nmol/min/（mg蛋白质）]。HLMs和UGT1A1中的岩白菜素葡萄糖醛酸基转移酶活性受到保泰松、雌二醇和胆红素的抑制。结果表明，HLMs中岩白菜素的葡萄糖醛酸化是由UGT1A1特异性催化的。
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