Melanin biosynthesis (Homo sapiens)
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Description
Melanin biosynthesis takes place in specialized cells called melanocytes, within membrane-bound organelles referred to as melanosomes. Melanosomes are transferred via dendrites to surrounding keratinocytes. Keratinocytes and melanocytes are collectively known as 'the epidermal melanin unit'. Each melanocyte is in contact with approximately 40 keratinocytes in the basal and suprabasal layers (Cichorek et al. 2013). Melanocytes are distributed in the epidermis, hair follicles, the inner ear and the eye (Yamaguchi et al. 2007, Tolleson 2005).
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 (Meredith & Riesz 2004) and to detoxify reactive oxygen species (ROS) (Bustamante et al. 1993), while pheomelanin is a phototoxic pro-oxidant (Samokhvalov 2005). Most natural melanin pigments contain eumelanin and pheomelanin (Ito & Wakamatsu 2003) and are termed 'mixed' melanins. Neuromelanins are mixed melanin-like pigments which are mainly found in neurons of the substantia nigra and locus coeruleus (Fedorow et al. 2005). Synthesis of NM may prevent the accumulation of toxic catechol derivatives (Zecca et al. 2003). NM can sequester a variety of potentially damaging molecules such as beta-carbolines, heavy metal ions and 1-methyl-4-phenylpyridinium (MPP+) (D'Amato et al. 1986), a drug which causes Parkinson's Disease-like symptoms. Models suggest that mixed melanogenesis occurs in three stages (Ito et al. 2000). 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 (Land et al. 2003). View original pathway at:Reactome.
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 (Meredith & Riesz 2004) and to detoxify reactive oxygen species (ROS) (Bustamante et al. 1993), while pheomelanin is a phototoxic pro-oxidant (Samokhvalov 2005). Most natural melanin pigments contain eumelanin and pheomelanin (Ito & Wakamatsu 2003) and are termed 'mixed' melanins. Neuromelanins are mixed melanin-like pigments which are mainly found in neurons of the substantia nigra and locus coeruleus (Fedorow et al. 2005). Synthesis of NM may prevent the accumulation of toxic catechol derivatives (Zecca et al. 2003). NM can sequester a variety of potentially damaging molecules such as beta-carbolines, heavy metal ions and 1-methyl-4-phenylpyridinium (MPP+) (D'Amato et al. 1986), a drug which causes Parkinson's Disease-like symptoms. Models suggest that mixed melanogenesis occurs in three stages (Ito et al. 2000). 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 (Land et al. 2003). View original pathway at:Reactome.
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The reactions beyond BT and BTCA which ultimately lead to the production of pheomelanin appear to be very complex (Di Donato & Napolitano 2003). Zn2+ promotes retention of the carboxyl group in BTCA while Fe3+ accelerates the ring contraction of BT to BZ (Di Donato et al. 2002). Production of ODHBT is increased by the presence of hydrogen peroxide (Di Donato et al. 2002).