Guowen Zhang, M. Zhu, Yi-jing Liao
Jun 21, 2022
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0
Influential Citations
4
Citations
Quality indicators
Journal
Journal of the science of food and agriculture
Abstract
BACKGROUND Tea polyphenols have been reported to have the effect of lowering uric acid. However, there are few studies on the inhibitory effects and molecular mechanisms of specific catechins on urate metabolizing enzyme xanthine oxidase (XO). In this research, multiple spectroscopic methods and computer simulations were used to determine the inhibitory ability and mechanisms of epigallocatechin gallate (EGCG) and gallocatechin gallate (GCG) on XO. RESULTS Herein, EGCG and GCG reversibly inhibited XO activity in a mixed manner with the IC50 values of 40.50 ± 0.32 and 33.60 ± 0.53 μM, and also decreased the superoxide anion radical (O2 - ) of the catalytic system by reducing XO molecule and inhibiting the formation of uric acid. The combination of EGCG or GCG with allopurinol showed the synergistic inhibition on XO. The binding of EGCG or GCG to XO with moderate affinity formed the stable complex by hydrogen bonds and van der Waals forces. The presence of EGCG and GCG made the structure of XO more stable and compact, two inhibitors bound to the vicinity of flavin adenine dinucleotide (FAD) in XO, hindering the entry of substrate, thus the activity of XO was suppressed. CONCLUSIONS Both EGCG and GCG are excellent natural XO inhibitors, and inhibit the activity of XO by occupying the channel of the substrate to enter the active center and interfering with the dual substrate reaction catalyzed by XO. These findings provide a scientific basis for the application of catechins in dietary supplements and medicines with lowering uric acid effects. This article is protected by copyright. All rights reserved.