Theoretical Approaches to the Evolutionary Optimization of Glycolysis

TLDR

The kinetic and thermodynamic properties of glycolysis are linked to its stoichiometry, particularly the number and placement of ATP‑coupling sites. The study investigates whether the contemporary structure of glycolysis can be explained by evolutionary optimization principles. A minimal model of unbranched energy‑converting pathways is extended to include internal feedback, variable enzyme concentrations, and aldolase‑step branching. The analysis shows that optimal ATP production requires both ATP‑producing and ATP‑consuming sites, that kinetic optimization can increase the rate, that concentrating ATP‑consuming sites at the beginning and ATP‑producing sites at the end maximizes the rate, and that the resulting optimal numbers of coupling sites match those observed in glycolysis.

Abstract

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.