Heinrich R, Montero F, Klipp E, Waddell T G, Meléndez-Hevia E
Humboldt-Universität zu Berlin, Mathematisch-Naturwissenschaftliche Fakultät I, Institut für Biologie, Germany.
Eur J Biochem. 1997 Jan 15;243(1-2):191-201. doi: 10.1111/j.1432-1033.1997.0191a.x.
It is analyzed whether the structural design of contemporary glycolysis can be explained theoretically on the basis of optimization principles originating from natural selection during evolution. Particular attention is paid to the problem of how the kinetic and thermodynamic properties of the glycolytic pathway are related to its stoichiometry with respect to the number and location of ATP-coupling sites. The mathematical analysis of a minimal model of unbranched energy-converting pathways shows that the requirement of high ATP-production rate favours a structural design that includes not only ATP-producing reactions (P-sites) but also ATP-consuming reactions (C-sites). It is demonstrated that, at fixed overall thermodynamic properties of a chain, the ATP-production rate may be enhanced by kinetic optimization. The ATP-production rate is increased if the C-sites are concentrated at the beginning and all the P-sites at the end of the pathway. An optimum is attained, which is characterized by numbers of coupling sites corresponding to those found in glycolysis. Various extensions of the minimal model are considered, which allow the effects of internal feedback-regulations, variable enzyme concentrations, and the symmetric branching of glycolysis at the aldolase step to be considered.
分析了当代糖酵解的结构设计是否能基于进化过程中自然选择产生的优化原则从理论上进行解释。特别关注糖酵解途径的动力学和热力学性质如何与其关于ATP偶联位点数量和位置的化学计量学相关的问题。对无分支能量转换途径的最小模型进行数学分析表明，高ATP产生速率的要求有利于一种结构设计，该设计不仅包括ATP产生反应（P位点），还包括ATP消耗反应（C位点）。结果表明，在链的固定总体热力学性质下，通过动力学优化可以提高ATP产生速率。如果C位点集中在途径的起始端，而所有P位点集中在末端，则ATP产生速率会增加。达到了一个最优状态，其特征是偶联位点的数量与糖酵解中发现的数量相对应。考虑了最小模型的各种扩展，这使得能够考虑内部反馈调节、可变酶浓度以及糖酵解在醛缩酶步骤的对称分支的影响。
