title: Human tyrosinase is able to oxidize both enantiomers of rhododendrol.
abstract: Racemic RS-4-(4-hydroxyphenyl)-2-butanol (rhododendrol, RD) was used as a topical skin-whitening agent until it was recently reported to induce leukoderma. We then showed that oxidation of RD with mushroom tyrosinase rapidly produces RD-quinone, which is quickly converted to RD-cyclic quinone and RD-hydroxy-p-quinone. In this study, we examined whether either or both of the enantiomers of RD can be oxidized by human tyrosinase. Using a chiral HPLC column, racemic RD was resolved optically to R(-)-RD and S(+)-RD enantiomers. In the presence of a catalytic amount of l-dopa, human tyrosinase, which can oxidize l-tyrosine but not d-tyrosine, was found to oxidize both R(-)- and S(+)-RD to give RD-catechol and its oxidation products. S(+)-RD was more effectively oxidized than l-tyrosine, while R(-)-RD was less effective. These results support the notion that the melanocyte toxicity of RD depends on its tyrosinase-catalyzed conversion to toxic quinones and the concomitant production of reactive oxygen species.
authors.affiliation: Department of Chemistry, Fujita Health University School of Health Sciences, Toyoake, Aichi, Japan.
authors.forename: Shosuke
authors.initials: S
authors.lastname: Ito
authors.forename: Wolfram
authors.initials: W
authors.lastname: Gerwat
authors.forename: Ludger
authors.initials: L
authors.lastname: Kolbe
authors.forename: Toshiharu
authors.initials: T
authors.lastname: Yamashita
authors.forename: Makoto
authors.initials: M
authors.lastname: Ojika
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Wakamatsu
mesh_terms: D000440:Butanols / Q000737:chemistry* / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006801:Humans; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D010084:Oxidation-Reduction; D013237:Stereoisomerism; D013997:Time Factors
chemical_list: D000440:Butanols; C115945:rhododendrol; D014442:Monophenol Monooxygenase
keywords: human tyrosinase; melanocyte toxicity; rhododendrol; whitening agent