Abstract:
Inosine triphosphate pyrophosphatase (ITPase) is an enzyme encoded by the ITPA gene and functions to prevent the incorporation of noncanonical purine nucleotides into DNA and RNA. Specifically, the ITPase catalyzed the hydrolysis of (deoxy) nucleoside triphosphates ((d) NTPs) into the corresponding nucleoside monophosphate with the concomitant release of pyrophosphate. Recently, thiopurine drug metabolites such as azathioprine have been included in the lists of ITPase substrates. Interestingly, inosine or xanthosine triphosphate (ITP/XTP) and their deoxy analogs, deoxy inosine or xanthosine triphosphate (dITP/dXTP), are products of important biological reactions such as deamination that take place within the cellular compartments. However, the incorporation of ITP/XTP, dITP/dXTP, or the genetic deficiency or polymorphism of the ITPA gene have been implicated in many human diseases, including infantile epileptic encephalopathy, early onset of tuberculosis, and the responsiveness of patients to cancer therapy. This review provides an up-to-date report on the ITPase enzyme, including information regarding its discovery, analysis, and cellular localization, its implication in human diseases including cancer, and its therapeutic potential, amongst others.
摘要:
三磷酸肌苷焦磷酸酶(ITPase)是由ITPA基因编码的酶,其功能是防止非规范嘌呤核苷酸掺入DNA和RNA中。具体来说,ITPase催化(脱氧)核苷三磷酸((d)NTP)水解为相应的核苷单磷酸,同时释放焦磷酸盐。最近,硫嘌呤药物代谢物如硫唑嘌呤已包括在ITPase底物列表中。有趣的是,肌苷或三磷酸黄苷(ITP/XTP)及其脱氧类似物,脱氧肌苷或三磷酸黄苷(dITP/dXTP),是重要的生物反应的产物,例如在细胞区室中发生的脱氨基作用。然而,ITP/XTP的合并,dITP/dXTP,或ITPA基因的遗传缺陷或多态性与许多人类疾病有关,包括婴儿癫痫性脑病,早发性肺结核,以及患者对癌症治疗的反应。这篇综述提供了关于ITPase酶的最新报告,包括关于它的发现的信息,分析,和细胞定位,它对包括癌症在内的人类疾病的影响,以及它的治疗潜力,在其他人中。