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首页> 外文期刊>The FEBS journal >Diadenosine tetraphosphate (Ap4A) - an E-coli alarmone or a damage metabolite?
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Diadenosine tetraphosphate (Ap4A) - an E-coli alarmone or a damage metabolite?

机译：二磷酸二磷酸酯（AP4A） - 一种e-coli angerone或损伤代谢物？

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摘要

Under stress, metabolism is changing: specific up- or down-regulation of proteins and metabolites occurs as well as side effects. Distinguishing specific stress-signaling metabolites (alarmones) from side products (damage metabolites) is not trivial. One example is diadenosine tetraphosphate (Ap4A) - a side product of aminoacyl-tRNA synthetases found in all domains of life. The earliest observations suggested that Ap4A serves as an alarmone for heat stress in Escherichia coli. However, despite 50 years of research, the signaling mechanisms associated with Ap4A remain unknown. We defined a set of criteria for distinguishing alarmones from damage metabolites to systematically classify Ap4A. In a nutshell, no indications for a signaling cascade that is triggered by Ap4A were found; rather, we found that Ap4A is efficiently removed in a constitutive, nonregulated manner. Several fold perturbations in Ap4A concentrations have no effect, yet accumulation at very high levels is toxic due to disturbance of zinc homeostasis, and also because Ap4A's structural overlap with ATP can result in spurious binding and inactivation of ATP-binding proteins. Overall, Ap4A met all criteria for a damage metabolite. While we do not exclude any role in signaling, our results indicate that the damage metabolite option should be considered as the null hypothesis when examining Ap4A and other metabolites whose levels change upon stress.
机译：在应力下，代谢正在发生变化：蛋白质和代谢物的特异性上调和下调以及副作用。区分特定的应力信号传导代谢物（Almarone）从侧面产品（损伤代谢物）并不琐碎。一个例子是一种实例的四磷酸盐（AP4A） - 在所有寿讯结构域中发现的氨基酰基-TRNA合成酶的副产物。最早的观察结果表明AP4A用作大肠杆菌中的热应激的恶性杆。然而，尽管研究了50年的研究，与AP4A相关的信令机制仍然未知。我们定义了一组用于区分警报从损伤代谢物中的标准，以系统地分类AP4A。简而言之，未发现由AP4A触发的信号级联的指示;相反，我们发现AP4A以本构体介质，非制造方式有效地除去。 AP4A浓度的几个折癌无效，然而，由于锌稳态的干扰，非常高水平的积累是毒性，并且由于AP4A与ATP的结构重叠可能导致ATP结合蛋白的杂散结合和失活。总体而言，AP4A符合损害代谢物的所有标准。虽然我们在信号传导中不排除任何作用，但我们的结果表明，当检查AP4A和其他质量变化的其他代谢物时，应将损伤代谢物选项视为零假设。

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