Regulatory mechanisms of melanogenesis: beyond the tyrosinase concept

The last decade has witnessed a quantum jump in our knowledge of the chemistry of melanogenesis and the emergence of some understanding as to how the chemical and enzymatic activities are integrated and regulated at cellular level. To an unusual extent, most of these advances stemmed from a molecular approach involving direct analysis of natural melanins coupled with studies of the chemical reactivity of the putative intermediates under biologically relevant conditions. Thus, bit by bit it has been possible to reconstruct in vitro the overall chemical activity of melanocytes, and to identify a number of regulatory factors other than tyrosinase. This and other approaches, especially the molecular biology of the pigment-related genes, have radically changed and expanded the traditional concept of melanogenesis far beyond the boundaries of the Raper-Mason pathway. Recently, I suggested an improved scheme of melanogenesis accounting for the formation of melanins and related products of melanocyte activity. The present contribution surveys some verifications of the predictions, and certain new break-throughs that have been made in the understanding of the regulatory steps after the dopaquinone stage. It also aims to provide an overview of what is presently known about the structure of the melanin polymers, and to draw attention to some problems pertaining to the definition and classification of the various types of pigments that can be found in epidermal tissues.