Melanogenesis inhibition by tetrahydropterines

Abstract

There is controversy in the literature concerning the action of tetrahydropterines on the enzyme tyrosinase and on melanogenesis in general. In this study, we demonstrate that tetrahydropterines can inhibit melanogenesis in several ways: i) by non-enzymatic inhibition involving purely chemical reactions reducing o-dopaquinone to L-dopa, ii) by acting as substrates which compete with L-tyr and L-dopa, since they are substrates of tyrosinase; and iii) by irreversibly inhibiting the enzymatic forms met-tyrosinase and deoxytyrosinase in anaerobic conditions. Three tetrahydropterines have been kinetically characterised as tyrosinase substrates: 6-R-L-erythro-5,6,7,8-tetrahydrobiopterin, 6-methyl-5,6,7,8-tetrahydropterine and 6,7-(R,S)-dimethyl-5,6,7,8-tetrahydropterine. A kinetic reaction mechanism is proposed to explain the oxidation of these compounds by tyrosinase.

Existe controversia en la literatura con respecto a la acción de las tetrahidrobiopterinas sobre la enzima tirosinasa y sobre la melanogénesis en general. En este estudio, demostramos que las tetrahidrobiopterinas pueden inhibir la melanogénesis de varias formas: i) mediante la inhibición no enzimática que implica reacciones puramente químicas reduciendo la o-dopaquinona a L-dopa, ii) actuando como sustratos que compiten con L-tirosina y L-dopa, ya que son sustratos de la tirosinasa; y iii) mediante la inhibición irreversible de las formas enzimáticas met-tirosinasa y deoxitirosinasa en condiciones anaeróbicas. Tres tetrahidrobiopterinas han sido caracterizadas cinéticamente como sustratos de la tirosinasa: 6-R-L-eritro-5,6,7,8-tetrahidrobiopterina, 6-metil-5,6,7,8-tetrahidropterina y 6,7-(R,S)-dimetil-5,6,7,8-tetrahidropterina. Se propone un mecanismo de reacción cinético para explicar la oxidación de estos compuestos por la tirosinasa.