Nucleoside exchange catalysed by the cytoplasmic 5'-nucleotidase.
Nucleoside exchange catalysed by the cytoplasmic 5'-nucleotidase.
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由细胞质 5-核苷酸酶催化的核苷交换。
作者：
Y. Worku;A. Newby
用部分纯化的大鼠肝脏酶制剂研究了其产物肌苷对细胞质5′-核苷酸酶（EC 3.1.3.5）的抑制作用。抑制Pi的产生是由于肌苷和IMP之间交换肌苷部分。交换不是通过水解反应的逆转来催化的，而是通过酶-磷酸盐中间体的介导。提出了两种催化机理模型，并推导了Pi生成对肌苷浓度依赖性的速率方程。实验确定的依赖性与酶-磷酸盐中间体只有在不被肌苷占据时才发生水解的机制一致。这一结论表明，肌苷类似物不能参与交换应该抑制酶。这些抑制剂可能有助于确定酶的生理作用或作为减少嘌呤核苷酸分解的药理学试剂。核苷交换为致突变或细胞毒性核苷类似物的磷酸化提供了另一种途径的可能性也应予以考虑。
The inhibition of the cytoplasmic 5'-nucleotidase (EC 3.1.3.5) by its product, inosine, was studied with a partially purified preparation of the enzyme from rat liver. Inhibition of Pi production was found to be due to exchange of the inosine moiety between inosine and IMP. Exchange was not catalysed by reversal of the hydrolytic reaction, suggesting, instead, the mediation of an enzyme-phosphate intermediate. Two models for the catalytic mechanism are proposed and rate equations for the dependence of Pi production on inosine concentration are derived. The experimentally determined dependence was consistent with a mechanism in which hydrolysis of the enzyme-phosphate intermediate occurred only when it was unoccupied by inosine. This conclusion suggests that inosine analogues that cannot participate in exchange should inhibit the enzyme. Such inhibitors might be useful in defining the enzyme's physiological role or as pharmacological agents to decrease breakdown of purine nucleotides. The possibility that nucleoside exchange provides an alternative route for the phosphorylation of mutagenic or cytotoxic nucleoside analogues should also be considered.