Theoretical approaches to the evolutionary optimization of glycolysis--chemical analysis

Abstract

In the first part of this work [Heinrich, R., Montero, F., Klipp, E., Waddell, T. G. & Melendez-Hevia, E. (1997) Eur. J. Biochem. 243, 191-201] the kinetic and thermodynamic constraints under which an optimal glycolysis must be designed have been analysed. In this second part, we present a chemical analysis of the glycolytic pathway in order to determine if its design is chemically optimized according the possibilities that a glycolytic design can have. Our results demonstrate that glycolysis in modern-day cells (from glucose to lactate) has an optimized design for maximizing the flux of ATP production, and a thermodynamic profile which guarantees a high kinetic efficiency. We also discuss some cases of paleometabolism for this pathway as alternative metabolic pathways, less optimized, that exist in some bacteria. Our analysis relates mainly to metabolism designed under constant chemical affinity (substrates and products of the pathway constant), where the target of optimization can be the flux of ATP production. We also discuss the case of an externally imposed input flux, whose target of optimization is the stoichiometric yield of ATP.