Analysis of Metabolic Stability under Environmental Perturbations Using a Kinetic Model

Cells robustly maintain metabolic function despite environmental fluctuations affecting reaction kinetics, yet kinetic models often exhibit fragility. We investigated this discrepancy by examining the effects of temperature changes on a kinetic model of Escherichia coli central metabolism. A gradual temperature decrease caused an abrupt transition to a state with sharply reduced ATP production efficiency, triggered by an elevated ATP/ADP ratio creating a glycolysis bottleneck. Introducing a rapid ATP-ADP exchange reaction prevented this ATP/ADP ratio surge and sustained high ATP production efficiency across temperatures. Furthermore, altering enzyme abundances similarly maintained high ATP production, with predicted enzyme regulation aligning with experimental observations in E. coli at low temperatures. Our findings indicate that balancing key cofactors, such as the ATP/ADP ratio, is crucial for preserving metabolic stability under environmental perturbations.