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 molecular mechanism of the depigmenting action, which is still very poorly understood, we have investigated the effect of HQ on the tyrosinase catalysed conversion of tyrosine to melanin. 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 oxidation 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 oxidised in the presence of tyrosine owing to the generation of catalytic amounts of dopa acting as cofactor of tyrosinase. Product analysis of HQ oxidation with tyrosinase in the presence of dopa showed the predominant formation in the early stages of hydroxybenzoquinone (HBQ), arising from enzymic hydroxylation and subsequent oxidation of HQ, along with lower amounts of benzoquinone (BQ). These results suggest that the depigmenting activity of HQ may partly be related to the ability of the compound to act as an alternate substrate of tyrosinase, thereby competing for tyrosine oxidation in active melanocytes.
Palumbo
A
A
Stazione Zoologica University of Naples, Italy.
d'Ischia
M
M
Misuraca
G
G
Prota
G
G
D016227:Benzoquinones / Q000737:chemistry / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D006873:Hydroquinones / Q000494:pharmacology*; D066298:In Vitro Techniques; D045563:Indolequinones; D007211:Indoles / Q000737:chemistry / Q000378:metabolism; D007700:Kinetics; D008543:Melanins / Q000096:biosynthesis*; D014442:Monophenol Monooxygenase / Q000037:antagonists & inhibitors*; D010084:Oxidation-Reduction; D011809:Quinones / Q000737:chemistry / Q000378:metabolism; D013056:Spectrophotometry, Ultraviolet; D014443:Tyrosine / Q000737:chemistry / Q000378:metabolism
D016227:Benzoquinones; D006873:Hydroquinones; D045563:Indolequinones; D007211:Indoles; D008543:Melanins; D011809:Quinones; C001123:dopachrome; C004532:quinone; D014443:Tyrosine; D014442:Monophenol Monooxygenase; C031927:hydroquinone