Glycolytic strategy as a tradeoff between energy yield and protein cost
Glycolytic strategy as a tradeoff between energy yield and protein cost
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DOI：
10.1073/pnas.1215283110
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发表时间：
2013-06-11
影响因子：
11.1
通讯作者：
Milo, Ron
中科院分区：
文献类型：
--
作者：
Flamholz, Avi;Noor, Elad;Milo, Ron
与教科书将糖酵解描述为在所有生命领域中保守的单一途径相反，并非所有的糖消耗生物体都使用经典的Embden-Meyerhoff-Parnass（EMP）糖酵解途径。脯氨酸葡萄糖代谢特别多样化，包括几种替代糖酵解途径，其中最常见的是Entner-Doudoroff（艾德）途径。艾德途径的普遍性令人困惑，因为它每葡萄糖仅产生一个ATP-是EMP途径的一半。我们认为，原核葡萄糖代谢的多样性可能反映了途径的能量（ATP）产量和催化途径通量所需的酶蛋白量之间的权衡。我们介绍了热力学和动力学分析途径的方法，并表明，艾德途径预计需要几倍的酶蛋白，以实现相同的葡萄糖转化率的EMP途径。通过基因组分析，我们进一步表明，原核生物使用不同的糖酵解途径取决于他们的能量供应。具体而言，能量剥夺的厌氧菌压倒性地依赖于EMP途径的较高ATP产量，而艾德途径在兼性厌氧菌中是常见的，并且在需氧菌中甚至更常见。除了证明蛋白质成本如何解释替代代谢策略的使用外，这项研究还说明了生物体环境与其所采用的代谢途径的热力学和生物化学性质之间的直接联系。
Contrary to the textbook portrayal of glycolysis as a single pathway conserved across all domains of life, not all sugar-consuming organisms use the canonical Embden-Meyerhoff-Parnass (EMP) glycolytic pathway. Prokaryotic glucose metabolism is particularly diverse, including several alternative glycolytic pathways, the most common of which is the Entner-Doudoroff (ED) pathway. The prevalence of the ED pathway is puzzling as it produces only one ATP per glucose-half as much as the EMP pathway. We argue that the diversity of prokaryotic glucose metabolism may reflect a tradeoff between a pathway's energy (ATP) yield and the amount of enzymatic protein required to catalyze pathway flux. We introduce methods for analyzing pathways in terms of thermodynamics and kinetics and show that the ED pathway is expected to require several-fold less enzymatic protein to achieve the same glucose conversion rate as the EMP pathway. Through genomic analysis, we further show that prokaryotes use different glycolytic pathways depending on their energy supply. Specifically, energy-deprived anaerobes overwhelmingly rely upon the higher ATP yield of the EMP pathway, whereas the ED pathway is common among facultative anaerobes and even more common among aerobes. In addition to demonstrating how protein costs can explain the use of alternative metabolic strategies, this study illustrates a direct connection between an organism's environment and the thermodynamic and biochemical properties of the metabolic pathways it employs.