Mechanism of inhibition of melanogenesis by hydroquinone

Hydroquinone (HQ) is one of the most effective inhibitors of melanogenesis in vitro and in vivo, and is widely used for the treatment of melanosis and other hyperpigmentary disorders. In an attempt to get some insight into the mol. mechanism of the depigmenting action, which is still very poorly understood, the effect of HQ on the tyrosinase catalyzed conversion of tyrosine to melanin was examd. Incubation of 0.5 mM tyrosine with 0.07 U/mL tyrosinase in phosphate buffer at pH 6.8 in the presence of 0.5 mM HQ led to no detectable melanin formation, due to the preferential oxidn. of HQ with respect to tyrosine (HPLC evidence). Kinetic investigations showed that HQ is a poorer substrate of tyrosinase than tyrosine; yet, it may be effectively oxidized in the presence of tyrosine owing to the generation of catalytic amts. of dopa acting as cofactor of tyrosinase. Product anal. of HQ oxidn. with tyrosinase in the presence of dopa showed the predominant formation in the early stages of hydroxybenzoquinone (HBQ), arising from enzymic hydroxylation and subsequent oxidn. of HQ, along with lower amts. of benzoquinone (BQ). These results suggest that the depigmenting activity of HQ may partly be related to the ability of the compd. to act as an alternate substrate of tyrosinase, thereby competing for tyrosine oxidn. in active melanocytes.