Enzyme promiscuity, metabolite damage, and metabolite damage control systems of the tricarboxylic acid cycle,The FEBS Journal

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Enzyme promiscuity, metabolite damage, and metabolite damage control systems of the tricarboxylic acid cycle
The FEBS Journal ( IF 5.5 ) Pub Date : 2020-03-18 , DOI: 10.1111/febs.15284
Thomas D. Niehaus ₁ , Katie B. Hillmann ₁

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Promiscuous enzymes and spontaneous chemical reactions can convert normal cellular metabolites into noncanonical or damaged metabolites. These damaged metabolites can be a useless drain on metabolism and may be inhibitory and/or reactive, sometimes leading to toxicity. Thus, mechanisms to prevent metabolite damage from occurring (metabolite damage preemption) or to convert damaged metabolites back to physiological forms (metabolite repair) are essential for sustained operation of metabolic networks. Some iconic examples of metabolite damage and its repair or preemption are associated with the tricarboxylic acid (TCA) cycle, and other metabolite damage control systems are likely to exist here due to the inherent promiscuity of TCA cycle enzymes and reactivity of TCA cycle intermediates. Here, we review known metabolite damage reactions and metabolite damage control systems associated with the TCA cycle. This includes a previously unrecognized metabolite damage control system – an oxaloacetate (OAA) enol‐keto tautomerase activity that is ‘built‐in’ to the TCA cycle. This activity is required to remove the highly inhibitory enol form of OAA and is likely to be critical for TCA cycle operation. By cataloging these instances, we show that metabolite damage and its repair or preemption is a prevalent feature of the TCA cycle and suggest many more metabolite damage control systems are likely to exist.

中文翻译：

三羧酸循环的酶混杂，代谢物破坏和代谢物破坏控制系统

混杂的酶和自发的化学反应可以将正常的细胞代谢物转化为非规范的或受损的代谢物。这些受损的代谢物可能会浪费掉新陈代谢，可能具有抑制性和/或反应性，有时会导致毒性。因此，防止代谢物损害发生（代谢物损害优先）或将受损的代谢物转化回生理形式（代谢物修复）的机制对于代谢网络的持续运行至关重要。代谢物破坏及其修复或抢占的一些标志性例子与三羧酸（TCA）循环有关，由于TCA循环酶固有的混杂性和TCA循环中间体的反应性，此处可能存在其他代谢物破坏控制系统。这里，我们回顾了与TCA周期相关的已知代谢物破坏反应和代谢物破坏控制系统。这包括以前无法识别的代谢物破坏控制系统-草酰乙酸（OAA）烯醇-酮互变异构酶活性，已内置于TCA循环中。该活性是去除OAA的高度抑制性烯醇形式所必需的，并且可能对TCA循环操作至关重要。通过对这些实例进行分类，我们显示出代谢物损害及其修复或抢占是TCA周期的普遍特征，并暗示可能存在更多的代谢物损害控制系统。该活性是去除OAA的高度抑制性烯醇形式所必需的，并且可能对TCA循环操作至关重要。通过对这些实例进行分类，我们显示出代谢物损害及其修复或抢占是TCA周期的普遍特征，并暗示可能存在更多的代谢物损害控制系统。该活性是去除OAA的高度抑制性烯醇形式所必需的，并且可能对TCA循环操作至关重要。通过对这些实例进行分类，我们显示出代谢物损害及其修复或抢占是TCA周期的普遍特征，并暗示可能存在更多的代谢物损害控制系统。

更新日期：2020-04-06

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