Court Steven J, Waclaw Bartlomiej, Allen Rosalind J
SUPA, School of Physics and Astronomy, University of Edinburgh, James Clerk Maxwell Building, Peter Guthrie Tait Road, Edinburgh EH9 3FD, UK.
Nat Commun. 2015 Sep 29;6:8427. doi: 10.1038/ncomms9427.
The universality of many pathways of core metabolism suggests a strong role for evolutionary selection, but it remains unclear whether existing pathways have been selected from a large or small set of biochemical possibilities. To address this question, we construct in silico all possible biochemically feasible alternatives to the trunk pathway of glycolysis and gluconeogenesis, one of the most highly conserved pathways in metabolism. We show that, even though a large number of alternative pathways exist, the alternatives carry lower flux than the real pathway under typical physiological conditions. We also find that if physiological conditions were different, different pathways could outperform those found in nature. Together, our results demonstrate how thermodynamic and biophysical constraints restrict the biochemical alternatives that are open to evolution, and suggest that the existing trunk pathway of glycolysis and gluconeogenesis may represent a maximal flux solution.
核心代谢的许多途径具有普遍性，这表明进化选择发挥了重要作用，但目前尚不清楚现有的途径是从大量还是少量的生化可能性中选择出来的。为了解决这个问题，我们通过计算机模拟构建了糖酵解和糖异生主干途径的所有可能的生化可行替代途径，糖酵解和糖异生是代谢中最保守的途径之一。我们发现，尽管存在大量替代途径，但在典型生理条件下，这些替代途径的通量低于真实途径。我们还发现，如果生理条件不同，不同的途径可能比自然界中发现的途径表现更好。总之，我们的结果证明了热力学和生物物理限制如何限制了可供进化选择的生化替代方案，并表明现有的糖酵解和糖异生主干途径可能代表了最大通量解决方案。
