Understanding the emergence of metabolic pathways is key to unraveling the factors that promoted the origin of life. One popular view is that protein cofactors acted as catalysts prior to the evolution of the protein enzymes with which they are now associated. We investigated the stability of acetyl coenzyme A (Acetyl Co-A, the group transfer cofactor in citric acid synthesis in the TCA cycle) under early Earth conditions, as well as whether Acetyl Co-A or its small molecule analogs thioacetate or acetate can catalyze the transfer of an acetyl group onto oxaloacetate in the absence of the citrate synthase enzyme. Several different temperatures, pH ranges, and compositions of aqueous environments were tested to simulate the Earth's early ocean and its possible components; the effect of these variables on oxaloacetate and cofactor chemistry were assessed under ambient and anoxic conditions. The cofactors tested are chemically stable under early Earth conditions, but none of the three compounds (Acetyl Co-A, thioacetate, or acetate) promoted synthesis of citric acid from oxaloacetate under the conditions tested. Oxaloacetate reacted with itself and/or decomposed to form a sequence of other products under ambient conditions, and under anoxic conditions was more stable; under ambient conditions the specific chemical pathways observed depended on the environmental conditions such as pH and presence/absence of bicarbonate or salt ions in early Earth ocean simulants. This work demonstrates the stability of these metabolic intermediates under anoxic conditions. However, even though free cofactors may be stable in a geological environmental setting, an enzyme or other mechanism to promote reaction specificity would likely be necessary for at least this particular reaction to proceed.

中文翻译：

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模型早期地球条件下代谢中间体的反应性和辅因子稳定性。

了解代谢途径的出现是弄清促进生命起源的因素的关键。一种流行的观点是，蛋白质辅因子在与之相关的蛋白质酶进化之前起着催化剂的作用。我们研究了在早期地球条件下乙酰辅酶A（乙酰辅酶A，TCA循环中柠檬酸合成中的基团转移辅助因子）的稳定性，以及乙酰辅酶A或其小分子类似物硫代乙酸盐或乙酸盐是否可以催化在没有柠檬酸合酶的情况下将乙酰基转移到草酰乙酸上。测试了几种不同的温度，pH范围和水性环境的成分，以模拟地球的早期海洋及其可能的组成部分。在环境和缺氧条件下评估了这些变量对草酰乙酸和辅因子化学的影响。所测试的辅因子在地球早期条件下化学稳定，但是在所测试的条件下，这三种化合物（乙酰基Co-A，硫代乙酸酯或乙酸酯）均未促进由草酰乙酸合成柠檬酸。草酰乙酸在室温下与自身反应和/或分解形成一系列其他产物，在缺氧条件下更稳定；在环境条件下，观察到的特定化学途径取决于环境条件，例如pH值以及地球早期海洋模拟物中是否存在碳酸氢盐或盐离子。这项工作证明了这些代谢中间体在缺氧条件下的稳定性。然而，