The novel mechanism on the inhibition of superoxide anion generating from xanthine oxidase in the presence of myricetin

• Published in: International journal of biological macromolecules 2024-12, Vol.283 (Pt 1), p.137636, Article 137636
• Main Authors: Yao, Yuanyong, Ma, Ao, Huang, Qi, Chen, Jiarong, Yan, Jiangzhou, Chen, Lihong, Ye, Jiaxing, Zhang, Meng, Yang, Hai, Chen, Shixue
• Format: Article
• Language: English
• Subjects: Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Flavonoids - chemistry; Flavonoids - metabolism; Flavonoids - pharmacology; Inhibition mechanism; Kinetics; Molecular Docking Simulation; Molecular Dynamics Simulation; Myricetin; Superoxide anion; Superoxides - chemistry; Superoxides - metabolism; Thermodynamics; Xanthine oxidase; Xanthine Oxidase - antagonists & inhibitors; Xanthine Oxidase - chemistry; Xanthine Oxidase - metabolism
• ISSN: 0141-8130; 1879-0003; 1879-0003
• DOI: 10.1016/j.ijbiomac.2024.137636

To gain an in-depth understanding of the process of myricetin (MY) inhibiting the generation of •O2− from Xanthine Oxidase (XOD) at a novel perspective, the inhibiting pathway is necessary to be re-elaborated through inhibitory type, thermodynamic analysis and molecular simulation. The results demonstrated that MY is indeed a potent inhibiting agent for •O2− producing from XOD, with the maximum value of 33.78 % in the inhibition of •O2−. Furthermore, the deprotonated form (De-MY) of MY was examined to be an effective agent for interacting with XOD, with the measurement of •O2− in productions from MY, XOD@MY and XAN-XOD@MY, as comparing to the XAN-XOD@ALL. On the inhibition kinetics, De-MY was witnessed to be on a mixed-type inhibition, with more competitive inhibition. In the thermodynamic analysis, the Stern-Volmer plots for De-MY obtained at 298 K, 303 K and 308 K, were polynomial-fitted to form curves approaching the X axis via the fluorescence quenching of XOD, which was against the reported with good linearity. It indicated that the interaction between De-MY and XOD occurred at the range of MY concentrations from 0 to 0.025 (×10−5 mol L−1), is dominated by a static quenching procedure, ascribing to the appearance of accessible interaction with corresponding f values less than 1. As well, via combining the synchronous fluorescence data, Molecular dynamics simulations showed that MY binding to the Trp 283, ARG-60 and Tyr 58 with H-binding interactions is an available access to block the transfer of free electrons from FADH2 to O2. Therefore, in this work, successfully re-elaborating the inhibition mechanism of •O2− generating from XOD by MY is benefited for MY in the future applications.