Scopoletin and Morin Inhibit Lactate Dehydrogenase Enzyme Activity, Which Is Critical for Cancer Metabolism

Background: Lactate dehydrogenase (LDH) is a tetrameric enzyme that catalyzes the interconversion of pyruvate to L-lactate. Theimportance of this enzyme is because LDH isoenzymes are involved in cancer, heart, and liver diseases. Inhibition of this enzymecan help prevent and treat different diseases. Morin is a flavonoid found in the Moraceae family and scopoletin is a coumarin foundin Scopolia genus.Objectives: The aim of this study was to determine the effect of morin and scopoletin as two natural products on the activity andstructure of lactate dehydrogenase enzyme.Methods: Morin and scopoletin were examined for inhibition of the activity of LDH in ۱۰۰mMsodium phosphate buffer pH ۷.۵, atroom temperature using UV-V spectrophotometry. Fluorescence spectroscopy was used to characterize protein structural changesin the presence of morin and scopoletin.Results: Km and Vmax of LDH for pyruvate were ۱۱.۶۹ mM and ۱.۲۵۸ mM/min, respectively. The kinetic results showed that morinand scopoletin are LDH inhibitors. The Ki values of morin and scopoletin were determined as ۱.۷۸ M and ۰.۸ M, respectively,using a secondary plot. Fluorescence intensity quenching and red shift of themaximumwavelength of emission in a concentrationdependentmanner showed that morin and scopoletin bind to LDH and affect its structure.Conclusions: The results suggest that morin and scopoletin bind to LDH, influence its conformation and inhibit its activity. Scopoletinshowed more effective inhibition of LDH activity and it can be a promising candidate in the field of tumor metabolism inhibitors.

کلیدواژه ها:

Lactate Dehydrogenase ، Morin ، Scopoletin ، Spectrophotometry ، Enzyme inhibitors