Effect of metal ions on the rearrangement of dopachrome.

In vitro experiments are reported showing that a number of transition metal ions exert a profound influence on both the kinetics and chemical course of the rearrangement of dopachrome, a key step in the biosynthesis of melanins. HPLC analysis shows that Cu2+, Ni2+ and Co2+ are particularly effective in inducing the non-decarboxylative rearrangement of dopachrome at physiological pH values, leading mainly to 5,6-dihydroxyindole-2-carboxylic acid, whereas in the absence of metal ions the reaction proceeds with concomitant loss of carbon dioxide to give almost exclusively 5,6-dihydroxyindole. Kinetic experiments provide evidence that the rate of the metal-promoted rearrangement is first order with respect to both aminochrome and metal concentration and decreases in the presence of increasing concentrations of EDTA, consistent with a mechanism involving a direct 1:1 dopachrome-metal ion interaction in the transition state. When considered in the light of the known metal accumulation in pigmented tissues, the results of this study provide a new entry into the regulatory mechanisms involved in the biosynthesis of melanins.