Rating metabolic pathways by enzyme efficiency
2023
Liebermeister, Wolfram | Noor, Elad | Mathématiques et Informatique Appliquées du Génome à l'Environnement [Jouy-En-Josas] (MaIAGE) ; Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE) | Weizmann Institute of Science [Rehovot, Israël] | The Economic Cell Collective
International audience
显示更多 [+] 显示较少 [-]英语. In this chapter we discuss why certain pathway designs have been selected by evolution, by hypothesizing that some are more beneficial than others-based on several possible criteria and optimization goals: minimizing the number of reactions, maximizing product yield, increasing reaction turnover rates, and avoiding small thermodynamic driving forces. It turns out that all these criteria are related to a single objective: minimizing enzyme demand per product production rate or, equivalently, maximizing "enzyme productivity". We first focus on simple unbranched pathways with predefined flux distributions. We discuss several feasibility and optimality problems where metabolite concentrations are independent variables and solve for the minimal enzyme demand. In this setting, we see how enzyme productivity can be assessed or predicted and how it depends on different system parameters such as kinetics, thermodynamics, and concentrations of enzymes and metabolites. We discuss the difference between growth rate and yield. We then illustrate it by comparing between pathway options for glycolysis.
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