Exploring the inhibitory effects of glutamic acid on melanin production: Mechanistic insights and molecular docking analysis

¹ Dept. of Public Health and Medical Technology, Xiamen Medical College, Xiamen 361023, Fujian, China
² School of Public Health, Fujian Medical University, Fuzhou, Fujian Province, China
³ Engineering Research Center of Natural Cosmeceuticals College of Fujian Province, Xiamen Medical College, Xiamen 361023, Fujian, China

^* Corresponding author: 3399248132@qq.com

Abstract

Glutamic acid is widely recognized as safe and has various applications in the medical and food industries. This study demonstrated its significant inhibition of tyrosinase, acting as a mixed-type inhibitor according to enzymatic kinetic analysis. Fluorescence spectroscopy analysis and investigation of tyrosinase activity under different pH confirmed that glutamic acid induced changes in the protein structure of tyrosinase, leading to its reduced activity through acidification and binding effects. Additionally, glutamic acid was found to inhibit L-DOPA auto-oxidation, thereby preventing further formation of dopachrome. The IC50 values for glutamic acid inhibiting tyrosinase activity and L-DOPA auto-oxidation were detected to be 4.69 mM and 0.72 mM, respectively. Glutamic acid had a better inhibitory effect on L-DOPA autooxidation than tyrosinase activity. The L-DOPA auto-oxidation process can also lead to the formation of melanin, and its inhibition by glutamic acid further supported its potential in controlling melanin synthesis. Moreover, glutamic acid demonstrated a dose-dependent decrease in melanin production in B16 cells while maintaining cell viability. Western blot analysis revealed decreased protein expression of TYR and TRP-1, both of which are involved in melanin production, with increasing concentrations of glutamic acid. Molecular docking analysis suggested a potential mechanism involving the disruption of copper binding sites on tyrosinase. These findings underscore the potential of glutamic acid as a promising agent for controlling melanin production and associated disorders.