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dc.contributor.authorWood, John M.*
dc.contributor.authorChavan, Bhavan*
dc.contributor.authorHafeez, Idris*
dc.contributor.authorSchallreuter, Karin U.*
dc.date.accessioned2009-09-29T07:29:49Z
dc.date.available2009-09-29T07:29:49Z
dc.date.issued2004
dc.identifier.citationWood, 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.identifier.urihttp://hdl.handle.net/10454/3531
dc.descriptionNoen
dc.description.abstractRecently 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.language.isoenen
dc.relation.isreferencedbyhttp://dx.doi.org/10.1016/j.bbrc.2004.10.185en
dc.subjectTyrosinaseen
dc.subjectTyrosineen
dc.subjectH2O2en
dc.subjectTetrahydrobiopterinen
dc.subjectMelanogenesisen
dc.titleRegulation of tyrosinase by tetrahydropteridines and H2O2.en
dc.status.refereedYesen
dc.typeArticleen
dc.type.versionNo full-text available in the repositoryen


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