PMID: 9540806Apr 16, 1998Paper

6-Tetrahydrobiopterin functions as a UVB-light switch for de novo melanogenesis

Biochimica Et Biophysica Acta
K U SchallreuterE R Werner

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.

References


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Citations

Jan 31, 2004·Biochemical and Biophysical Research Communications·Jae Hyung JungSanghwa Han
Dec 18, 2001·Journal of Photochemistry and Photobiology. B, Biology·K U Schallreuter, J M Wood
Aug 22, 2009·Biochimica Et Biophysica Acta·F García-MolinaJ N Rodríguez-López
Aug 18, 2004·Biochemical and Biophysical Research Communications·Karin U SchallreuterJohn M Wood
May 11, 2005·Biochemical and Biophysical Research Communications·John M WoodKarin U Schallreuter
Nov 24, 2004·Biochemical and Biophysical Research Communications·John M WoodKarin U Schallreuter
Apr 30, 2014·Photochemistry and Photobiology·Andrey A BuglakMikhail S Kritsky
Nov 13, 2007·Free Radical Biology & Medicine·Karin U SchallreuterJohn M Wood
Aug 5, 2000·The Journal of Pathology·D J TobinK U Schallreuter
Sep 24, 2004·Physiological Reviews·Andrzej SlominskiJacobo Wortsman
Oct 3, 1998·Experimental Dermatology·K SchallreuterB A Gilchrest
Oct 21, 2000·Endocrine Reviews·A Slominski, J Wortsman
Dec 8, 2020·Free Radical Research·Andrey A BuglakMikhail S Kritsky

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