Melanogenesis in Skin and Hair

Melanogensis occurs by a common biochemical pathway in both the hair follicle and the epidermis [26-28]. Two types of melanin are found in the skin and hair, the brown/black melanin, eumelanin, and the red melanin, pheomelanin [26]. The formation of eumelanin begins with either hydroxylation of intracellular L-phenylalanine or from extracellular tyrosine transported into the cell (Fig. 8.1). L-phenylalanine is hydroxylated to L-tyrosine by the enzyme phenylalanine hydroxylase [29,30] . Phenylalnine hydroxylase requires (6R)-L-erythro 5,6,7,8 tetrahydrobiopterin as a cofactor [29]. 6BH4 may act as an allosteric inhibitor of tyrosinase and its abiogenic isomer, 7BH4, may inhibit PAH [30]. Melanin is also synthesized directly from intracellular L-tyrosine [31, 32]. L-tyrosine is hydroxylated to L-3,4-dihydroxyphenylalanine (L-dopa) by tyrosinase or tyrosine hydrox­ylase isoform I [33,34]. In the eumelanogenic pathway, tyrosinase is the most important enzyme for melanin synthesis [35] . L-dopa can also be formed from the reduction of L-dopaquinone back to L-dopa [32]. This is followed by the oxidation of L-dopa to dop – aquinone [35]. Melanogenesis will go through oxido-reduction reactions and intramolecu­lar transformations spontaneously, once L-dopa is formed [28]. The rate of these reactions are determined by local concentrations of hydrogen ions, metal cations, thiols, and the other reducing agents, hydrogen peroxide, and oxygen [35].

Synthesis of pheomelanin starts with the formation of cysteinyldopa from dopaqui – none and cysteine [36]. Cysteinyldopa can also be formed from the hydrolysis of glutathio – nyldopa by glutamyltranspeptidase [37 ] . Cysteinyldopa is then oxidized to yield 1,4- benzothiazinylalanines. The velocity of post-cysteinyldopa steps of melanogenesis is increased by peroxidase and tyrosinase, which are involved in the transformation of benzothiazinyla – lanines. The main regulatory mechanism switch from eu – to pheomelanogenesis employs dopaquinone as a key molecule controlling the activity of glutathione reductase. Pheomel – anogenesis is also blocked at high tyrosinase activity and high eumelanogenesis rate [36,37].

Both eumelanogenic and pheomelanogenic melanosomes can coexist in the same human cell [38], but not within the same melanosome [39]. Four processes have been used to explain the transfer of melanin granules from the melanosome to keratinocytes of the hair or skin: phagocytosis of the tips of dendrites containing melanosomes, internalization by the keratinocytes, the fusion of plasma membranes, and the transfer of melanosomes to the keratinocytes [40,41].

Updated: September 17, 2015 — 4:16 pm