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

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 acP53_317-320 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.