6-TETRAHYDROBIOPTERIN FUNCTIONS AS A UVB-LIGHT SWITCH FOR DE-NOVO MELANOGENESIS

(6R)-L-erythro 5,6,7,8-tetrahydrobiopterin (6-BH4)and its 7-isomer (7- BH4) function as uncompetitive inhibitors of human and mushroom tyrosi nases. Stoichiometry for the binding of [H-3]-labeled 6-BH, to both ty rosinases has been established as 1:1. Stable complexation of 6-BH4 to tyrosinase appears to involve a hydrophilic conserved glutamic acid ( Glu(131)) with a pK(a) = 4.7. Photo-oxidation by UVB-light and O-2 rev erses the inhibition of tyrosinase by 6-BH4 and 7-BH4 with the 6-BH4/t yrosinase complex being four-fold more photolabile than 7-BH4/tyrosina se. The photo-oxidation of 6-BH4 by UVB-light can be assessed spectrop hotometrically with this reaction yielding 7,8-dihydroxanthopterin as the final product. 7,8-Dihydroxanthopterin neither binds to nor inhibi ts tyrosinase. By contrast, UVA light does not catalyze the photodegra dation of 6-BH4. Taken together, our results indicate that the photo-o xidation of the tetrahydrobiopterins by UVB may represent a photo-swit ch in the regulation of tyrosinase activity to promote de novo melanog enesis. (C) 1998 Elsevier Science B.V.