Metabolic rate constants: Some computational aspects

Abstract

In this work we pose the question how reliable the Michaelis constant is as an enzyme kinetic parameter in situations when the Michaelis–Menten equation is not a good approximation of the true substrate dynamics as it may be in the case of metabolic processes in living cells. We compare the Michaelis–Menten substrate–product kinetics with the complete substrate–enzyme–product kinetics induced by the reaction scheme originally proposed by V. Henri. The Henri reaction scheme involves four concentrations and three rate constants and via the law of mass action is translated to a system of four ordinary differential equations (denoted as HMM-system). We propose a method for the computation of the three HMM rate constants, which can be applied in any situation whenever time course measurement data are available. The proposed method has been tested on the case study of acetylcholine hydrolysis. Our approach provides for the validation of the HMM-system by taking into account the uncertainties in the measurement data, and focuses on the use of contemporary computational tools.