Melanin biosynthesis

Melanocytes in mammals and birds produce two chemically distinct types of melanin, black to brown eumelanin and yellow to reddish-brown pheomelanin (Ito & Wakamatsu 2008, Simon et al. 2009, d'Ischia et al. 2013). These differ in their responses to UV radiation; eumelanin has the ability to convert absorbed light energy into heat energy and to detoxify reactive oxygen species (ROS), while pheomelanin is a phototoxic pro-oxidant. Most natural melanin pigments contain eumelanin and pheomelanin and are termed 'mixed' melanins. Neuromelanins are mixed melanin-like pigments which are mainly found in neurons of the substantia nigra and locus coeruleus. Synthesis of NM may prevent the accumulation of toxic catechol derivatives. NM can sequester a variety of potentially damaging molecules such as beta-carbolines, heavy metal ions and 1-methyl-4-phenylpyridinium (MPP+), a drug which causes Parkinson's Disease-like symptoms. Models suggest that mixed melanogenesis occurs in three stages. The initial stage of melanin biosynthesis is the production of cysteinyldopas, which continues while sufficient cysteine is available. The second stage is the oxidation of cysteinyldopas to produce pheomelanin, which continues while cysteinyldopa concentration is sufficiently high. The last stage is the production of eumelanin, which begins when cysteinyldopas and cysteine are depleted. The ratio of eumelanin to pheomelanin is determined by tyrosinase activity and the availability of tyrosine and cysteine.