Identification of a novel human uridine phosphorylase
Identification of a novel human uridine phosphorylase
复制标题
DOI：
10.1016/s0006-291x(03)01062-3
复制
发表时间：
2003-07-18
影响因子：
3.1
通讯作者：
Johansson, M
中科院分区：
文献类型：
--
作者：
Johansson, M
尿苷磷酸化酶催化尿苷和脱氧尿苷可逆的磷酸化裂解为尿嘧啶和核糖-或脱氧核糖-1-磷酸。该酶在用于癌症化疗的嘧啶类似物的代谢中起着重要作用。克隆了一种新的317个氨基酸的人尿苷磷酸化酶的cdna，它与先前发现的人尿苷磷酸化酶有近60%的同源性。该酶被命名为尿苷磷酸化酶-2(UPase-2)，具有广泛的底物特异性，可接受尿苷、脱氧尿苷、胸腺嘧啶核苷以及两种嘧啶核苷类似物5-氟尿苷和5-氟-2‘-脱氧尿苷。人UPase-2基因定位于染色体2q24.1，2.2kb的mRNA主要在肾脏表达。小鼠UPase-2基因也被鉴定出来，并且主要在肝脏中表达。一种新的具有广泛底物特异性的尿苷磷酸化酶的鉴定对于研究核苷代谢以及研究治疗性嘧啶核苷类似物的药理机制都具有重要意义。(C)2003年埃尔塞维尔科学公司(美国)。版权所有。
Uridine phosphorylase catalyzes the reversible phosphorylytic cleavage of uridine and deoxyuridine to uracil and ribose- or deoxyribose-1-phosphate. The enzyme has an important role in the metabolism of pyrimidine analogs used in cancer chemotherapy. The cDNA of a novel 317 amino acid human uridine phosphorylase; approximate to60% identical to the previously identified human uridine phosphorylase was cloned. The novel enzyme, named uridine phosphorylase-2 (UPase-2), showed broad substrate specificity and accepted uridine, deoxyuridine, and thymidine as well as the two pyrimidine nucleoside analogs 5-fluorouridine and 5-fluoro-2'-deoxyuridine. The human UPase-2 gene was mapped to chromosome 2q24.1 and the 2.2-kb mRNA was predominantly expressed in kidney. The mouse UPase-2 cDNA was also identified and shown to be predominantly expressed in liver. The identification of a novel uridine phosphorylase with broad substrate specificity is important for studies on both nucleoside metabolism as well as for studies on the pharmacological mechanisms of therapeutic pyrimidine nucleoside analogs. (C) 2003 Elsevier Science (USA). All rights reserved.