PRPS1基因及其突变与相关临床综合征的研究进展

Research progress of PRPS1 gene and its mutations and related clinical syndrome

PRPS1基因编码的磷酸核糖焦磷酸合成酶(PRS)1是参与核酸合成的第一限速酶,其对细胞功能,特别是嘌呤、嘧啶相关的合成、代谢等有重要影响。当PRPS1基因突变引起PRS1晶体结构改变时,其编码的PRS1活性也将发生改变,进而不仅会导致嘌呤和嘧啶代谢紊乱,还会引起细胞能量代谢紊乱。此外,遗传性PRPS1基因突变会引起高耗能组织器官的功能异常,出现一系列的临床综合征。在肿瘤患者中也存在体细胞的PRPS1基因突变,可引起肿瘤耐药复发。总之,PRS1在能量代谢、细胞信号转导及核酸合成等方面发挥关键作用,对维持人体正常生理活动具有重要意义。笔者拟就PRPS1基因编码的PRS1在人体的生理功能和晶体结构、PRPS1基因及其突变对细胞代谢的调节及PRPS1基因突变相关临床综合征等方面进行综述。

Phosphoribosyl pyrophosphate synthetase(PRS)1,encoded by PRPS1 gene,is the first limiting enzyme participating in the synthetic process of nucleic acids.Consequently,it has a great effect on cell functions,especially the synthesis and metabolism of purine and pyrimidine.Some changes in PRS1 crystal structure might exert inconceivable effects on enzyme activity and lead to disorder of purine/pyrimidine metabolism,even cellular energy metabolism failure.Inherited mutation may induce disfunction of some energy-intensive tissue,the common clinical manifestations are some clinical syndrome.In addition,PRPS1 mutations found in cancer are proved to be an important cause of tumor resistance,followed by patient relapse.In a word,PRS1 plays a key role in energy metabolism,signal transduction and nucleic acid synthesis,which is of great significance in maintaining physiological activities.This article mainly focuses on the physiological functions and crystal structure of PRS1,the regulation of cell metabolism by PRPS1 gene and its mutations,as well as clinical syndromes related to PRPS1 gene mutation.