A prebiotic basis for ATP as the universal energy currency.
A prebiotic basis for ATP as the universal energy currency.
复制标题
DOI：
10.1371/journal.pbio.3001437
复制
发表时间：
2022-10
期刊：
影响因子：
9.8
通讯作者：
中科院分区：
文献类型：
--
作者：
ATP作为细胞中的主要能量货币普遍保守，通过磷酸化和缩合反应驱动新陈代谢。如此深层次的保守性表明，ATP出现在生物化学进化的早期阶段。然而，嘌呤合成需要6个磷酸化步骤，与ATP水解有关。ATP合成ATP的这种自催化要求意味着需要更早的益生元ATP等价物，其可以在嘌呤合成之前驱动蛋白质代谢。为什么这种早期的磷酸化剂被替换，特别是用ATP而不是其他核苷三磷酸，仍然是一个谜。在这里，我们表明，ATP的深度保护可能反映了其与另一种普遍保守的中间体乙酰磷酸（AcP）有关的益生元化学，该中间体通过将乙酰辅酶A连接到ADP的底物水平磷酸化来连接硫酯和磷酸盐代谢之间的桥梁。我们证实了早期的结果表明，在水中的Fe3+离子的存在下，AcP可以磷酸化ADP ATP在近20%的产率。然后，我们表明，Fe 3+和ACP是令人惊讶的青睐。广泛的prebiotically相关的离子和矿物质未能催化ADP磷酸化。从一组益生元磷酸化剂中，只有AcP和较小程度的氨基甲酰磷酸盐显示出任何显著的磷酸化潜力。重要的是，AcP不磷酸化任何其他核苷二磷酸。我们使用这些数据，反应动力学和分子动力学模拟来推断可能的机制。我们的研究结果可能表明，ATP在整个生命中普遍保守的原因是，在温和的益生元条件下，它的形成在水溶液中是化学上有利的。这项研究表明，乙酰磷酸盐是唯一的一个大面板中的合理的益生元代理磷酸化ADP ATP在水中的三价铁的存在下。乙酰磷酸不会磷酸化其他核苷二磷酸，这表明ATP在水中的不寻常化学基础上，成为益生元单体世界中的通用能量货币。
ATP is universally conserved as the principal energy currency in cells, driving metabolism through phosphorylation and condensation reactions. Such deep conservation suggests that ATP arose at an early stage of biochemical evolution. Yet purine synthesis requires 6 phosphorylation steps linked to ATP hydrolysis. This autocatalytic requirement for ATP to synthesize ATP implies the need for an earlier prebiotic ATP equivalent, which could drive protometabolism before purine synthesis. Why this early phosphorylating agent was replaced, and specifically with ATP rather than other nucleoside triphosphates, remains a mystery. Here, we show that the deep conservation of ATP might reflect its prebiotic chemistry in relation to another universally conserved intermediate, acetyl phosphate (AcP), which bridges between thioester and phosphate metabolism by linking acetyl CoA to the substrate-level phosphorylation of ADP. We confirm earlier results showing that AcP can phosphorylate ADP to ATP at nearly 20% yield in water in the presence of Fe3+ ions. We then show that Fe3+ and AcP are surprisingly favoured. A wide range of prebiotically relevant ions and minerals failed to catalyse ADP phosphorylation. From a panel of prebiotic phosphorylating agents, only AcP, and to a lesser extent carbamoyl phosphate, showed any significant phosphorylating potential. Critically, AcP did not phosphorylate any other nucleoside diphosphate. We use these data, reaction kinetics, and molecular dynamic simulations to infer a possible mechanism. Our findings might suggest that the reason ATP is universally conserved across life is that its formation is chemically favoured in aqueous solution under mild prebiotic conditions. This study shows that acetyl phosphate is unique among a large panel of plausible prebiotic agents in phosphorylating ADP to ATP in water in the presence of ferric iron. Acetyl phosphate does not phosphorylate other nucleoside diphosphates, suggesting that ATP became established as the universal energy currency in a prebiotic, monomer world on the basis of its unusual chemistry in water.
影响因子：
2
作者：
Kaye, Karl;Bryant, David E.;Marriott, Katie E. R.;Ohara, Shohei;Fishwick, Colin W. G.;Kee, Terence P.
通讯作者：
Kee, Terence P.