Abstract

Glycolysis is a metabolic pathway vital to the production of energy and some organisms rely on it solely to meet their energy requirements. It is also a central pathway in the metabolism of carbohydrates and a source of therapeutic targets against diabetes and cancer. Caffeoylquinic acids (CQAs) have been extensively studied for their role in the treatment and prevention of diabetes (and cancer) but their mechanisms of action remain mostly unknown. As such, molecular docking was used to find possible targets of CQAs in the glycolysis pathway. The molecular docking assays showed that CQAs were docked preferably to the Rossman fold (nicotinamide adenine dinucleotide — NAD(H) binding site) of oxidoreductases, that use NAD(H) as a cofactor, than to any other site. In-vitro assays were then performed using two NAD(H) dependent oxidoreductases from glycolysis (alcohol dehydrogenase and L-lactate dehydrogenase) in order confirm if CQAs would compete with the cofactor to inhibit the reaction. The results from these assays indicate that CQAs can act as both inhibitors and activators of NAD(H) dependent oxidoreductases of the glycolysis pathway.

Highlights

  • Glycolysis was the first major metabolic pathway to be fully understood (Lenzen, 2014)

  • Considering the docking results and the limited availability of diCQAs two enzymes of this type that were potentially inhibited by different Caffeoylquinic acids (CQAs) were chosen for the in-vitro assays

  • Most of the results from the kinetic assays showed that the regression of the reactions where CQAs were present intercepted the uninhibited reaction well inside the first quadrant of the Lineweaver-Burk plots

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Summary

Introduction

Glycolysis was the first major metabolic pathway to be fully understood (Lenzen, 2014). This pathway has many steps that lead to the catabolism of glucose and other hexoses into pyruvate (Pelicano et al, 2006; Bar-Even et al, 2012). The pathway diverges depending on the availability of oxygen. NADH (nicotinamide adenine dinucleotide) is converted to NAD+ (Pelicano et al, 2006; Bolaños et al, 2010; Bar-Even et al, 2012).

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