Mojarrabi B, Mackenzie P I
Department of Clinical Pharmacology, Flinders University of South Australia, Bedford Park.
Biochem Biophys Res Commun. 1997 Sep 29;238(3):775-8. doi: 10.1006/bbrc.1997.7388.
The cDNA encoding the UDP glucuronosyltransferase, UGT1A10, has been cloned from human colon. The deduced amino acid sequence of the cDNA is 90% similar in sequence to that of a previously characterized form, UGT1A9 (Hlug P4), and contains a signal peptide and carboxyl-terminal hydrophobic domain characteristic of all UDP glucuronosyltransferases isolated to date. The enzyme synthesized in UGT1A10 cDNA-transfected COS-7 cells has a relative molecular mass of 56 kDa and is very active in the glucuronidation of mycophenolic acid (apparent Km of 34 microM and Vmax of 0.6 nmoles/min/mg protein). Other UGTs (UGT1A1, 1A3, 1A4, 1A6, 1A9, 2B7, 2B10 and 2B11) synthesized in COS cells had relatively little activity towards mycophenolic acid, suggesting that UGT1A10 may have a significant role in the elimination of this antineoplastic and immunosuppressive agent in vivo.
编码尿苷二磷酸葡萄糖醛酸基转移酶UGT1A10的cDNA已从人结肠中克隆出来。该cDNA推导的氨基酸序列与先前鉴定的UGT1A9（Hlug P4）形式的序列有90%的相似性，并且包含一个信号肽和羧基末端疏水结构域，这是迄今为止分离出的所有尿苷二磷酸葡萄糖醛酸基转移酶的特征。在转染了UGT1A10 cDNA的COS-7细胞中合成的酶相对分子质量为56 kDa，并且在霉酚酸的葡萄糖醛酸化反应中非常活跃（表观Km为34 microM，Vmax为0.6纳摩尔/分钟/毫克蛋白质）。在COS细胞中合成的其他UGT（UGT1A1、1A3、1A4、1A6、1A9、2B7、2B10和2B11）对霉酚酸的活性相对较低，这表明UGT1A10可能在体内消除这种抗肿瘤和免疫抑制剂中起重要作用。
