Regulation of tyrosinase by tetrahydropteridines and H2O2.
|dc.contributor.author||Wood, John M.||*|
|dc.contributor.author||Schallreuter, Karin U.||*|
|dc.identifier.citation||Wood, J.M., Chavran, B, Hafeez, I and Schallreuter, K.U. (2004). Regulation of tyrosinase by tetrahydropteridines and H2O2. Biochemical and Biophysical Research Communications. Vol. 325, No. 4, pp. 1412-1417.||en|
|dc.description.abstract||Recently two alternative mechanisms have been put forward for the inhibition of tyrosinase by 6R-l-erythro 5,6,7,8-tetrahydrobiopterin (6BH4). Initially allosteric uncompetitive inhibition was demonstrated due to 1:1 binding of 10¿6 M 6BH4 to a specific domain 28 amino acids away from the CuA active site of the enzyme. Alternatively it was then shown that 10¿3 M 6BH4 inhibit the reaction by the reduction of the product dopaquinone back to l-dopa. In the study presented herein we have used two structural analogues of 6BH4 (i.e., 6,7-(R,S)-dimethyl tetrahydrobiopterin and 6-(R,S)-tetrahydromonapterin) confirming classical uncompetitive inhibition due to specific binding of the pyrimidine ring of the pterin moiety to the regulatory domain on tyrosinase. Under these conditions there was no reduction of l-dopaquinone back to l-dopa by both cofactor analogues. Inhibition of tyrosinase by 6BH4 occurs in the concentration range of 10¿6 M after preactivation with l-tyrosine and this mechanism uncouples the enzyme reaction producing H2O2 from O2. Moreover, a direct oxidation of 6BH4 to 7,8-dihydrobiopterin by tyrosinase in the absence of the substrate l-tyrosine was demonstrated. The enzyme was activated by low concentrations of H2O2 (<0.3 × 10¿3 M), but deactivated at concentrations in the range 0.5¿5.0 × 10¿3 M. In summary, our results confirm a major role for 6BH4 in the regulation of human pigmentation.||en|
|dc.title||Regulation of tyrosinase by tetrahydropteridines and H2O2.||en|
|dc.type.version||No full-text available in the repository||en|