New insight into molecular mechanisms of different polyphenols affecting Sirtuin 3 deacetylation activity

Yulong Wei; Yiman Zhang; Ziyuan Wang; Zihui Yang; Zongwei Wang; Yiming Hao; Genying Li; Fei Gao; Gaoqi Ye; Jing Wang; Jie Liu

doi:10.1016/j.ijbiomac.2024.132026

New insight into molecular mechanisms of different polyphenols affecting Sirtuin 3 deacetylation activity

Int J Biol Macromol. 2024 May 3;270(Pt 1):132026. doi: 10.1016/j.ijbiomac.2024.132026. Online ahead of print.

Authors

Yulong Wei¹, Yiman Zhang¹, Ziyuan Wang¹, Zihui Yang¹, Zongwei Wang¹, Yiming Hao¹, Genying Li¹, Fei Gao¹, Gaoqi Ye¹, Jing Wang², Jie Liu³

Affiliations

¹ Key Laboratory of Geriatric Nutrition and Health, Beijing Technology and Business University, Ministry of Education, Beijing 100048, China; National Center of Technology Innovation for Grain Industry (Comprehensive Utilization of Edible by-products), Beijing Technology and Business University, Beijing 100048, China.
² Key Laboratory of Geriatric Nutrition and Health, Beijing Technology and Business University, Ministry of Education, Beijing 100048, China; National Center of Technology Innovation for Grain Industry (Comprehensive Utilization of Edible by-products), Beijing Technology and Business University, Beijing 100048, China. Electronic address: wangjing@th.btbu.edu.cn.
³ Key Laboratory of Geriatric Nutrition and Health, Beijing Technology and Business University, Ministry of Education, Beijing 100048, China; National Center of Technology Innovation for Grain Industry (Comprehensive Utilization of Edible by-products), Beijing Technology and Business University, Beijing 100048, China. Electronic address: liu_jie@btbu.edu.cn.

PMID: 38704074
DOI: 10.1016/j.ijbiomac.2024.132026

Abstract

Multiple phenolic substances have been shown to promote SIRT3 expression, however, few studies have focused on the effects of these phenolics on SIRT3 enzyme activity. This study constructed a variety of reaction systems to elucidate the mechanisms by which different polyphenols affect SIRT3 enzyme activity. The results showed that acP53₃₁₇_-₃₂₀ was the most suitable substrate among the five acetylated peptide substrates (K_cat/K_m = 74.85 ± 1.86 M^-1•s^-1). All the phenolic compounds involved in the experiment inhibited the enzymatic activity of SIRT3, and the lowest IC₅₀ among them was quercetin (0.12 ± 0.01 mM) and the highest was piceatannol (1.29 ± 0.08 mM). Their inhibition types were mainly competitive and mixed. In addition, piceatannol was found to be a natural SIRT3 agonist by enzyme kinetic analysis and validation of deacetylation efficiency. This study will provide a useful reference for polyphenol modulation of SIRT3 dosage, as well as the development and application of polyphenol-based SIRT3 activators and agonists.

Keywords: Deacetylation activity; Polyphenols; SIRT3.