Pathway: Melanin biosynthesis
Reactions in pathway: Melanin biosynthesis :
Melanin biosynthesis
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).
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).
Cellular metabolism of amino acids and related molecules includes the pathways for the catabolism of amino acids, the biosynthesis of the nonessential amino acids (alanine, arginine, aspartate, asparagine, cysteine, glutamate, glutamine, glycine, proline, and serine) and selenocysteine, the synthesis of urea, and the metabolism of carnitine, creatine, choline, polyamides, melanin, and amine-derived hormones. The metabolism of amino acids provides a balanced supply of amino acids for protein synthesis. In the fasting state, the catabolism of amino acids derived from breakdown of skeletal muscle protein and other sources is coupled to the processes of gluconeogenesis and ketogenesis to meet the body’s energy needs in the absence of dietary energy sources. These metabolic processes also provide the nitrogen atoms for the biosynthesis of nucleotides and heme, annotated as separate metabolic processes (Felig 1975; Häussinger 1990; Owen et al. 1979).
Transport of these molecuels across lipid bilayer membranes is annotated separately as part of the module on "transmembrane transport of small molecules".
Metabolic processes in human cells generate energy through the oxidation of molecules consumed in the diet and mediate the synthesis of diverse essential molecules not taken in the diet as well as the inactivation and elimination of toxic ones generated endogenously or present in the extracellular environment. The processes of energy metabolism can be classified into two groups according to whether they involve carbohydrate-derived or lipid-derived molecules, and within each group it is useful to distinguish processes that mediate the breakdown and oxidation of these molecules to yield energy from ones that mediate their synthesis and storage as internal energy reserves. Synthetic reactions are conveniently grouped by the chemical nature of the end products, such as nucleotides, amino acids and related molecules, and porphyrins. Detoxification reactions (biological oxidations) are likewise conveniently classified by the chemical nature of the toxin.
At the same time, all of these processes are tightly integrated. Intermediates in reactions of energy generation are starting materials for biosyntheses of amino acids and other compounds, broad-specificity oxidoreductase enzymes can be involved in both detoxification reactions and biosyntheses, and hormone-mediated signaling processes function to coordinate the operation of energy-generating and energy-storing reactions and to couple these to other biosynthetic processes.