Pathway Thermodynamics Highlights Kinetic Obstacles in Central Metabolism
Figure 1
The Flux-Force Efficacy and Minimum Optimized Driving-Force (MDF).
(A) A functional relationship between the reaction driving force (−ΔrG′) and its Flux-Force Efficacy, as described in detail in the Methods section. (B) Schematic comparison between two pathways. Each pathway starts and ends with the same compounds, employs five enzymes and carries the same net flux. The kinetic parameters of all enzymes in both pathways, as well as enzyme and metabolite concentrations, are assumed to be identical. (C) Energetic profile of Embden-Meyerhof-Parnas glycolysis. Dashed black line corresponds to ΔrG′o values (metabolite concentrations of 1 M) of pathway reactions at pH 7.5. Red line corresponds to ΔrG′ values of pathway reactions after an optimization procedure that maximizes the driving force of the reactions having the lowest driving forces, as described in the Methods section.