Indirect oxidation of 6-tetrahydrobiopterin by tyrosinase

Biochem Biophys Res Commun. 2004 Feb 20;314(4):937-42. doi: 10.1016/j.bbrc.2003.12.184.

Abstract

6-Tetrahydrobiopterin is known to bind to an allosteric site of tyrosinase to directly inhibit the enzyme. However, simultaneous measurements of ultraviolet-visible absorption spectra and oxygen consumption led us to conclude that the inhibition was due to oxidation of 6-tetrahydrobiopterin by dopaquinone. Immediately after addition of 6-tetrahydrobiopterin, tyrosinase stopped producing dopachrome from either tyrosine or dopa. Duration of inhibition was proportional to the concentration of added 6-tetrahydrobiopterin and the enzyme activity was fully restored after the inhibition. Surprisingly, there was a rapid consumption of oxygen during the inhibition period. In addition, absorption spectra indicated that the only reaction that occurred during the inhibition was oxidation of 6-tetrahydrobiopterin to 7,8-dihydrobiopterin. In the absence of tyrosine or dopa, tyrosinase did not oxidize 6-tetrahydrobiopterin, suggesting that a reaction intermediate between dopa and dopachrome was a target for the inhibition. We propose a new mechanism in which dopa is oxidized to dopaquinone and the latter, instead of producing dopachrome, is reduced back to dopa by 6-tetrahydrobiopterin.

MeSH terms

  • Biopterins / analogs & derivatives*
  • Biopterins / metabolism*
  • Dihydroxyphenylalanine / metabolism
  • Monophenol Monooxygenase / antagonists & inhibitors
  • Monophenol Monooxygenase / metabolism*
  • Oxidation-Reduction
  • Spectrophotometry, Ultraviolet
  • Substrate Specificity

Substances

  • Biopterins
  • Dihydroxyphenylalanine
  • Monophenol Monooxygenase
  • sapropterin