New thermodynamic activity-based approach allows predicting the feasibility of glycolysis

Thorsten Greinert,Thomas Maskow,Kristina Vogel,Christoph Held

doi:10.1038/s41598-021-85594-8

Thorsten Greinert, Thomas Maskow + Show 2 more

Open Access

https://doi.org/10.1038/s41598-021-85594-8

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Abstract

Thermodynamic feasibility analyses help evaluating the feasibility of metabolic pathways. This is an important information used to develop new biotechnological processes and to understand metabolic processes in cells. However, literature standard data are uncertain for most biochemical reactions yielding wrong statements concerning their feasibility. In this article we present activity-based equilibrium constants for all the ten glycolytic reactions, accompanied by the standard reaction data (standard Gibbs energy of reaction and standard enthalpy of reaction). We further developed a thermodynamic activity-based approach that allows to correctly determine the feasibility of glycolysis under different chosen conditions. The results show for the first time that the feasibility of glycolysis can be explained by thermodynamics only if (1) correct standard data are used and if (2) the conditions in the cell at non-equilibrium states are accounted for in the analyses. The results here will help to determine the feasibility of other metabolisms and to understand metabolic processes in cells in the future.

Highlights

Thermodynamic feasibility analyses help evaluating the feasibility of metabolic pathways
The Q term is often assumed to be the ratio of the metabolite concentrations; that is, activity coefficients of the metabolites are ignored in most analyses
The reason behind this are that the activity coefficients of the metabolites are not equal to one, neither is their ratio, which is required in the Q term

Summary

Introduction

Thermodynamic feasibility analyses help evaluating the feasibility of metabolic pathways. New standard data (especially Rg0 ) for glycolytic reactions have been accessed by equilibrium concentrations[12,13,14,15,16,17,18,19,20,21,22,23,24,25,26] combined with thermodynamic modeling[12, 17, 18, 22,23,24, 26] In these works, it was proven that the equilibrium concentrations of glycolytic reactions strongly depend on the medium conditions. Wangler et al determined Kγ with ePC-SAFT at measured metabolite equilibrium concentration in order to calculate Ka and an activity-based Rg0 for the PGK reaction

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