A reanalysis of the foundations of the macromolecular rate theory

Abstract. The macromolecular rate theory (MMRT) has been proposed as a mechanistic scheme to describe the temperature dependence of enzymatic reactions, and has enjoyed quite some popularity recently. MMRT was motivated by assuming that enzyme denaturation is not sufficient to explain the decline of enzyme activity above an optimal temperature, and was derived with two experimental assumptions: (1) the half saturation parameter is independent of temperature; and (2) when the substrate concentration is kept at 10 times of the half saturation parameter at reference temperature, the enzyme assays are substrate saturated under all experimental temperatures. We show that both the motivating and experimental assumptions do not hold under many conditions. Consequently, the MMRT estimated temperature sensitivity of the maximum catalysis rate is inaccurate. It can mischaracterize temperature-related biochemical behaviors, such as inferring the existence of a unique optimal temperature where biochemical rate peaks, and the shift of this optimal temperature as an indicator of thermal acclimation or adaptation. We recommend that chemical kinetics theory is a better candidate for mechanistic modeling of the temperature dependence of biogeochemical rates.