Mechanistic Insights into Tyrosinase-Catalyzed Metabolism of Hydroquinone: Implications for the Etiology of Exogenous Ochronosis and Cytotoxicity to Melanocytes
- Author: mycolabadmin
- 11/4/2025
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Summary
Hydroquinone is a common ingredient in skin-lightening products that works through enzyme-mediated chemical reactions. This research revealed how an enzyme called tyrosinase processes hydroquinone through different chemical pathways, ultimately producing melanin-like compounds. The study found that long-term hydroquinone use may cause a darkening side effect called exogenous ochronosis through continued enzyme activity, and identified a new chemical marker to track this process.
Background
Hydroquinone (HQ) is widely used in skin-lightening products but its detailed metabolic pathways by tyrosinase remain incompletely understood. Despite therapeutic value, HQ is associated with adverse effects, particularly exogenous ochronosis (EO), a condition characterized by bluish-black hyperpigmented patches in treated areas.
Objective
This study aims to elucidate the mechanistic insights into tyrosinase-catalyzed metabolism of HQ, specifically focusing on the pathways leading to production of HQ-eumelanin (HQ-EM) and HQ-pheomelanin (HQ-PM) and their implications for exogenous ochronosis.
Results
Mushroom tyrosinase catalyzes hydroxylation of HQ to 2-hydroxyhydroquinone (HHQ) via the HBQ pathway producing HQ-EM. In the presence of cysteine, a shift to the BQ pathway occurs producing HQ-PM. 4-Aminophenol (AP) was identified as a novel marker of HQ-PM degradation, with HQ functioning as both a pseudo-substrate and true substrate for tyrosinase.
Conclusion
HQ serves dual roles in tyrosinase metabolism through both HBQ and BQ pathways, challenging the notion of HQ as a simple tyrosinase inhibitor. Continuous HQ oxidation mediated by tyrosinase may contribute to exogenous ochronosis through formation of low-molecular metabolites that potentially induce dermal polymerization.
- Published in:International Journal of Molecular Sciences,
- Study Type:Experimental/Biochemical Study,
- Source: 10.3390/ijms262110734, PMID: 41226769