5-磷酸核糖 1,5-二磷酸生物合成
中文名称
通路描述
5'-磷酸-alpha-D-核糖 1,5-二磷酸（PRPP）是嘌呤和嘧啶合成从头途径和补救途径中的关键中间体。PRPP 和负责其合成的酶活性最早由 Kornberg 等人（1955）描述。该酶，磷酸核糖焦磷酸合酶 1，已从人类红细胞纯化并生化表征。纯化的酶容易形成多聚体；其最小的活性形式似乎是一个二聚体，为简便起见，此处将其标注为二聚体。它特异性地催化从 ATP 或 dATP 转移焦磷酸到 D-核糖 5-磷酸，并且对 Mg++和正磷酸盐有绝对需求（Fox 和 Kelley 1971; Roth 等人 1974）。体内与 dATP 反应的显著性尚不清楚，因为细胞质中 dATP 的浓度通常远低于 ATP。该酶对体内嘌呤合成的重要性已通过证明在尿酸产生率持续异常高的个体中，磷酸核糖焦磷酸合酶活性过剩，与酶水平升高或酶性质改变相关（Becker 和 Kim 1987; Roessler 等人 1993）确立。分子克隆研究揭示了存在两个额外的基因，编码磷酸核糖焦磷酸合酶样蛋白，一个广泛表达（磷酸核糖焦磷酸合酶 2）和一个其表达似乎局限于睾丸（磷酸核糖焦磷酸合酶 1 样 1）（Taira 等人 1989; 1991）。这两种蛋白质均未纯化并生化表征，也未将这两种蛋白质丰度或序列的变化与人类核苷酸代谢的改变联系起来（Roessler 等人 1993; Becker 等人 1996），因此，基于其预测的氨基酸序列相似性，此处推断其二聚化和催化从 D-核糖 5-磷酸合成 PRPP 的能力。
英文描述
5-Phosphoribose 1-diphosphate biosynthesis 5-Phospho-alpha-D-ribose 1-diphosphate (PRPP) is a key intermediate in both the de novo and salvage pathways of purine and pyrimidine synthesis. PRPP and the enzymatic activity responsible for its synthesis were first described by Kornberg et al. (1955). The enzyme, phosphoribosyl pyrophosphate synthetase 1, has been purified from human erythrocytes and characterized biochemically. The purified enzyme readily forms multimers; its smallest active form appears to be a dimer and for simplicity it is annotated as a dimer here. It specifically catalyzes the transfer of pyrophosphate from ATP or dATP to D-ribose 5-phosphate, and has an absolute requirement for Mg++ and orthophosphate (Fox and Kelley 1971; Roth et al. 1974). The significance of the reaction with dATP in vivo is unclear, as the concentration of cytosolic dATP is normally much lower than that of ATP. The importance of this enzyme for purine synthesis in vivo has been established by demonstrating excess phosphoribosyl pyrophosphate synthetase activity, correlated with elevated enzyme levels or altered enzyme properties, in individuals whose rates of uric acid production are constitutively abnormally high (Becker and Kim 1987; Roessler et al. 1993).Molecular cloning studies have revealed the existence of two additional genes that encode phosphoribosyl pyrophosphate synthetase-like proteins, one widely expressed (phosphoribosyl pyrophosphate synthetase 2) and one whose expression appears to be confined to the testis (phosphoribosyl pyrophosphate synthetase 1-like 1) (Taira et al. 1989; 1991). Neither of these proteins has been purified and characterized enzymatically, nor have variations in the abundance or sequence of either protein been associated with alterations in human nucleotide metabolism (Roessler et al. 1993; Becker et al. 1996), so their dimerization and ability to catalyze the synthesis of PRPP from D-ribose 5-phosphate are inferred here on the basis of their predicted amino acid sequence similarity to phosphoribosyl pyrophosphate synthetase 1.
所含基因
3 个基因