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Phosphoribosyl Diphosphate (PRPP): Biosynthesis, Enzymology, Utilization, and Metabolic Significance.
Microbiology and Molecular Biology Reviews ( IF 8.0 ) Pub Date : 2016-12-30 , DOI: 10.1128/mmbr.00040-16
Bjarne Hove-Jensen 1, 2 , Kasper R Andersen 2 , Mogens Kilstrup 3 , Jan Martinussen 3 , Robert L Switzer 4 , Martin Willemoës 5
Affiliation  

Phosphoribosyl diphosphate (PRPP) is an important intermediate in cellular metabolism. PRPP is synthesized by PRPP synthase, as follows: ribose 5-phosphate + ATP → PRPP + AMP. PRPP is ubiquitously found in living organisms and is used in substitution reactions with the formation of glycosidic bonds. PRPP is utilized in the biosynthesis of purine and pyrimidine nucleotides, the amino acids histidine and tryptophan, the cofactors NAD and tetrahydromethanopterin, arabinosyl monophosphodecaprenol, and certain aminoglycoside antibiotics. The participation of PRPP in each of these metabolic pathways is reviewed. Central to the metabolism of PRPP is PRPP synthase, which has been studied from all kingdoms of life by classical mechanistic procedures. The results of these analyses are unified with recent progress in molecular enzymology and the elucidation of the three-dimensional structures of PRPP synthases from eubacteria, archaea, and humans. The structures and mechanisms of catalysis of the five diphosphoryltransferases are compared, as are those of selected enzymes of diphosphoryl transfer, phosphoryl transfer, and nucleotidyl transfer reactions. PRPP is used as a substrate by a large number phosphoribosyltransferases. The protein structures and reaction mechanisms of these phosphoribosyltransferases vary and demonstrate the versatility of PRPP as an intermediate in cellular physiology. PRPP synthases appear to have originated from a phosphoribosyltransferase during evolution, as demonstrated by phylogenetic analysis. PRPP, furthermore, is an effector molecule of purine and pyrimidine nucleotide biosynthesis, either by binding to PurR or PyrR regulatory proteins or as an allosteric activator of carbamoylphosphate synthetase. Genetic analyses have disclosed a number of mutants altered in the PRPP synthase-specifying genes in humans as well as bacterial species.

中文翻译:

磷酸二磷酸核糖酯(PRPP):生物合成,酶学,利用和代谢意义。

磷酸二磷酸核糖酯(PRPP)是细胞代谢中的重要中间体。PRPP由PRPP合酶合成,如下所示:核糖5-磷酸+ ATP→PRPP + AMP。PRPP普遍存在于活生物体中,并用于糖苷键形成的取代反应中。PRPP被用于生物合成嘌呤和嘧啶核苷酸,氨基酸组氨酸和色氨酸,辅因子NAD和四氢甲蝶呤,阿拉伯糖基单磷酸去甲肾上腺素和某些氨基糖苷类抗生素。审查了PRPP在这些代谢途径中的每一种的参与。PRPP合成酶的核心是PRPP合成酶,已通过经典的机械方法从生活的各个王国对它进行了研究。这些分析的结果与分子酶学的最新进展以及对真细菌,古细菌和人类的PRPP合成酶的三维结构的阐明相一致。比较了五种二磷酰基转移酶的催化结构和机理,以及二磷酰基转移,磷酰基转移和核苷酸基转移反应的所选酶的结构和机理。PRPP被大量的磷酸核糖基转移酶用作底物。这些磷酸核糖基转移酶的蛋白质结构和反应机制各不相同,并证明了PRPP作为细胞生理学中间体的多功能性。系统发育分析表明,PRPP合酶似乎在进化过程中源自磷酸核糖基转移酶。PRPP,此外,通过结合PurR或PyrR调节蛋白或作为氨基甲酰磷酸合成酶的变构活化剂,是嘌呤和嘧啶核苷酸生物合成的效应分子。遗传分析已经揭示了在人类以及细菌物种中,PRPP合酶特异性基因中的许多突变体。
更新日期:2019-11-01
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