标题： 代谢货币耦合中的热力学成本-可控性权衡 显示英文标题

标题： Thermodynamic cost-controllability tradeoff in metabolic currency coupling

摘要： 细胞代谢由多种货币代谢物如ATP、GTP和NAD(P)H等全局调控。这些代谢物在带电（高能）和不带电（低能）状态之间循环，以介导能量传递。 虽然不同的货币代谢物与不同的代谢功能相关，但它们的带电和不带电形式通常通过生化反应如${\rm ATP{\,+\,}GDP{\,\rightleftharpoons\,}ADP{\,+\,}GTP}$和$\rm NADP^+{\,+\,}NADH{\,\rightleftharpoons\,}NADPH{\,+\,}NAD^+ $互相转换。 因此，它们的能量状态通常是耦合的，并相互影响，这会阻碍不同货币代谢物的独立调控。 尽管对单个货币代谢物的分子生物学有广泛的认识，但仍然不清楚各种耦合货币代谢物的协调如何塑造代谢调控、效率以及最终的生物进化。 在这里，我们提出一个代谢货币耦合的最小理论模型，并揭示了代谢可控性与热力学成本之间的基本权衡关系：增加独立调控多个货币代谢物的能力通常需要这些代谢物的相当丰富的数量，而这又会导致更高的熵产生率。 这种权衡表明，在复杂环境中，生物进化倾向于使货币代谢物具有相等的丰富度，以提高代谢可控性，但付出更高的热力学成本；相反，在简单环境中，生物进化则使其具有不平衡的数量以减少热量耗散。 这些考虑也提出了关于核苷酸池平衡和基因组GC含量进化趋势的假设。 显示英文摘要

摘要： Cellular metabolism is globally regulated by various currency metabolites such as ATP, GTP, and NAD(P)H. These metabolites cycle between charged (high-energy) and uncharged (low-energy) states to mediate energy transfer. While distinct currency metabolites are associated with different metabolic functions, their charged and uncharged forms are generally interchangeable via biochemical reactions such as ${\rm ATP{\,+\,}GDP{\,\rightleftharpoons\,}ADP{\,+\,}GTP}$ and $\rm NADP^+{\,+\,}NADH{\,\rightleftharpoons\,}NADPH{\,+\,}NAD^+ $. Thus, their energetic states are generally coupled and influence each other, which would hinder the independent regulation of different currency metabolites. Despite the extensive knowledge of the molecular biology of individual currency metabolites, it remains poorly understood how the coordination of various coupled currency metabolites shapes metabolic regulation, efficiency, and ultimately the evolution of organisms. Here, we present a minimal theoretical model of metabolic currency coupling and reveal a fundamental tradeoff relationship between metabolic controllability and thermodynamic cost: increasing the capacity to independently regulate multiple currency metabolites generally requires comparable abundances of those metabolites, which in turn incurs a higher entropy production rate. The tradeoff suggests that in complex environments, organisms evolutionarily favor an equal abundance of currency metabolites to enhance metabolic controllability at the expense of a higher thermodynamic cost; conversely, in simple environments, organisms evolve to have imbalanced amounts of them to reduce heat dissipation. These considerations also offer a hypothesis regarding evolutionary trends in nucleotide-pool balance and genomic GC content.