title: 6-Tetrahydrobiopterin functions as a UVB-light switch for de novo melanogenesis.
abstract: (6R)-L-erythro 5,6,7,8-tetrahydrobiopterin (6-BH4) and its 7-isomer (7-BH4) function as uncompetitive inhibitors of human and mushroom tyrosinases. Stoichiometry for the binding of [3H]-labeled 6-BH4 to both tyrosinases has been established as 1:1. Stable complexation of 6-BH4 to tyrosinase appears to involve a hydrophilic conserved glutamic acid (Glu131) with a pKa = 4.7. Photo-oxidation by UVB-light and O2 reverses the inhibition of tyrosinase by 6-BH4 and 7-BH4 with the 6-BH4/tyrosinase complex being four-fold more photolabile than 7-BH4/tyrosinase. The photo-oxidation of 6-BH4 by UVB-light can be assessed spectrophotometrically with this reaction yielding 7,8-dihydroxanthopterin as the final product, 7,8-Dihydroxanthopterin neither binds to nor inhibits tyrosinase. By contrast, UVA light does not catalyze the photodegradation of 6-BH4. Taken together, our results indicate that the photo-oxidation of the tetrahydrobiopterins by UVB may represent a photo-switch in the regulation of tyrosinase activity to promote de novo melanogenesis.
authors.affiliation: Department of Biomedical Sciences, University of Bradford, West Yorks, UK. K.Schallreuter@bradford.ac.uk
authors.forename: K U
authors.initials: KU
authors.lastname: Schallreuter
authors.forename: J M
authors.initials: JM
authors.lastname: Wood
authors.forename: C
authors.initials: C
authors.lastname: Körner
authors.forename: K M
authors.initials: KM
authors.lastname: Harle
authors.forename: V
authors.initials: V
authors.lastname: Schulz-Douglas
authors.forename: E R
authors.initials: ER
authors.lastname: Werner
mesh_terms: D001487:Basidiomycota / Q000201:enzymology; D001665:Binding Sites / Q000502:physiology; D001708:Biopterins / Q000031:analogs & derivatives* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008543:Melanins / Q000096:biosynthesis*; D014442:Monophenol Monooxygenase / Q000378:metabolism*; D010782:Photolysis; D011485:Protein Binding; D014466:Ultraviolet Rays; D014976:Xanthopterin / Q000031:analogs & derivatives / Q000096:biosynthesis / Q000378:metabolism
chemical_list: C015148:7,8-dihydroxyxanthopterin; D004791:Enzyme Inhibitors; D008543:Melanins; D001708:Biopterins; D014442:Monophenol Monooxygenase; C003402:sapropterin; D014976:Xanthopterin