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Keywords:

  • Dopachrome;
  • 5,6-Dihydroxyindole-2-carboxylic acid;
  • Brown melanin;
  • Melanin enzymology

Dopachrome, an intermediate in melanin biosynthesis, exhibits some unusual properties. At physiologic pH (e.g., pH 6-8) it is unstable and spontaneously loses its carboxyl group to form 5,6-dihydroxyindole (DHI(and CO2. However, over this same pH range, if various metals or a melanocyte-specific enzyme are present, it rapidly rearranges to its isomer form—5,6-dihydroxyindole-2-carboxylic acid (DHICA)—which is far more stable than dopachrome in its ability to retain the carboxyl group. Whether or not the carboxyl group is retained could have important implications for the regulation of melanogenesis, since in the presence of oxygen DHI spontaneously forms a black precipitate, whereas DHICA forms a golden-brown solution. The solubility of “DHICA-melanin” is due to the presence of carboxyl groups, which provide negative charges and hydrophilicity. Thus, in vivo, the extent to which dopachrome is converted to DHI or DHICA may well influence the solubility and color of the melanin formed. The purpose of this article is to review recent findings in these areas and to discuss the possible significance of dopachrome conversion in the regulation of melanogenesis and color formation.

SUMMARY

This review has explored events in the melanogenic pathway that are under regulatory control after the formation of dopachrome. No attempt was made to include the regulation of pheomelanin synthesis, although the same basic questions should exist for both pheo- and eumelanogenesis. It seems clear that the earlier concepts of melanogenesis, wherein tyrosinase was the only regulatory enzyme, are incorrect, at least for mammals. Elucidating the newly described pathways will take considerable research effort and ingenuity over the coming years.