Data-driven model of glycolysis identifies the role of allostery in maintaining ATP homeostasis

Abstract

The specific roles of allostery in regulating metabolism are not well understood. Here, we develop a data-driven mathematical model of mammalian glycolysis that uses enzyme rate equations and coupled ordinary differential equations. The key components of our model are the rate equations for allosterically regulated enzymes based on the Monod-Wyman-Changeux model that we derive using a rigorous analysis of thousands of in vitro kinetic measurements. The resulting model recapitulates the properties of glycolysis observed in live cells and shows that the specific function of allosteric regulation is to maintain high and stable concentrations of ATP, while glycolysis without allosteric regulation is fully capable of producing ATP and ensuring that ATP hydrolysis generates energy. Our data-based modeling approach provides a roadmap for a better understanding of the role of allostery in metabolism regulation.