Phosphoenolpyruvate (PEP) is a important high-energy metabolite in processes such as glycolysis, gluconeogenesis and other relevant metabolic pathways. PEP plays key roles in modern metabolism thus a full understanding of how it was formed is necessary to gain more information about the evolution of the first metabolic processes. Previous studies suggest us that PEP-like compounds may have played a role in primitive phosphorylation pathways, possibly preceding enzymatic catalysis.
This study focuses on the analysis of the reaction pathway that leads to the formation of phosphoenolpyruvate under prebiotic conditions. The main goal is to calculate the energy barrier, which will allow to calculate the kinetics of these reactions. We focus on reactions such as aldol condensation, elimination and phosphorylation process.
In the research we use computational chemistry methods to model PEP reaction networks. For this purpose we work with the ORCA software and density functional theory (DFT) to determine energy barriers and transition states of reaction. In the calculation we take into account the aqueous phase and different pH values.
The calculations focus on locating transition states for different reaction stages and also on determining energy barriers for the subsequent stages from the PEP reaction network. Preliminary calculations indicate that the aldol condensation of glycolaldehyde to glyceraldehyde proceeds with a moderate energy barrier. The current study extends this approach by investigating the phosphorylation of glycolaldehyde and the subsequent aldol condensation of glycolaldehyde phosphate with formaldehyde to form glyceraldehyde-2-phosphate. Determining the energy barriers for these reactions will provide insights into the feasibility of PEP formation under prebiotic conditions.
A full understanding of the energetic properties of PEP formation under prebiotic conditions contributes to a broader discussion of the evolution of early metabolic pathways. The results of this study may help clarify how quickly phosphoenolpyruvate could be formed and under what conditions it can take place. Future research will additionally focus on including amino acids in the reaction network.