Raper-Mason scheme

In the Raper-Mason scheme of melanin biosynthesis (Fig. 5) 216, 217), tyrosine is enzymatically converted via dopa to dopaquinone. The subsequent oxidation steps leading to melanin formation depend upon the biochemical environment of the reaction site. However, the melanization process in vitro or in vivo has two important features the rearrangement of dopachrome and the oxidative polymerization of 5,6-dihydroxyindoles leading to melanochrome. 

According to Pawelek et al. 200), the biosynthesis of melanin in Cloudman melanoma cells is a complex process and is regulated by three factors (a) a dopamine conversion factor which converts dopamine to 5,6-dihydroxyindole (13), (b) a 5,6-dihydroxyindole conversion factor which catalyzes the conversion of 5,6-dihydroxyindole to melanin and is active when cells are exposed to melanotropin (MSH), and (c) a 5,6-dihydroxyindole blocking factor which restricts melanogenesis at the 5,6-dihydroxyindole stage. They have also shown that at least three steps in the Raper-Mason scheme of melanin formation from tyrosine are catalysed by tyrosinase (Fig. 6). 

Because both tryptophan and tyrosine participate in melanogenic processes, the possible influence of different enzymes like tyrosinase, tryptophan pyrrolase (TP), indoleamine 2,3-dioxygenase (lOD), and tyrosine aminotransferase (TAT) on the regulation of melanin synthesis as it relates to vitiligo has been depicted in Fig. 8, which constitutes a modification of the Raper-Mason scheme for melanin synthesis (53, 54). 

The over-simplifications inherent in the Raper-Mason scheme for melanin formation (Figure 4.14) have been emphasised by degrada-tive and biogenetic studies from a number of different laboratories. 

Nicolaus [10] and Mason [11] have described our current knowledge of the structure of melanic pigments, the most preponderant pigments of human hair. Two theories are still considered for the structure of melanin, and both consider structures involved in Raper s scheme (Figure 4-26) [54, 55], as intermediates in the formation of all melanic pigments. Nicolaus [56] has proposed that melanin is a complex random polymer (Figure 4-27), formed from several species of the Raper scheme. This is the favored scheme at this time. 

Electrochemical mechanistic studies of melanin are an outcome of melanin research in 1980. Various authors have employed these methods using various catecholamines and related compounds as substrates (52,106, 224, 285, 286, 287). These studies have not only confirmed the validity of Raper-Mason s scheme of melanogenesis (see page 158 Fig. 5) but also provided information regarding the mechanism of the chemical steps that occur in the early stages of the melanization process, the identification of each electron-transfer process, and the determination of the rate constants of non-oxidative reactions. 

Chakraborty DP, Roy S, Chakraborty AK, Rakshit R (1989) Tryptophan Participation in Melanogenesis Modification of Raper-Mason-Powelek Scheme of Melanin Formation. J Ind Chem Soc 66 699... 

Oxidative polymerization of phenol derivatives is also important pathway in vivo, and one example is the formation of melanin from tyrosine catalyzed by the Cu enzyme, tyrosinase. The pathway from tyrosine to melanin is described by Raper (7) and Mason (8) as Scheme 8 the oxygenation of tyrosine to 4-(3,4-dihydro-xyphenyl)-L-alanin (dopa), its subsequent oxidation to dopaqui-none, its oxidative cyclization to dopachrome and succeeding decarboxylation to 5,6-dihydroxyindole, and the oxidative coupling of the products leads to the melanin polymer. The oxidation of dopa to melanin was attempted here by using Cu as the catalyst. 

Several publications on electrochemical mechanistic studies of the oxidative transformations of catecholamines followed the contribution by R. N. Adam s group (256) and involved a-methyldopamine, a-methylnor-adrenaline, dopamine (257), a-methyldopa, 5,6-dihydroxy-2-methylin-dole (255), and dopa (259). These studies (257) (Scheme 5), which confirmed the validity of the melanization scheme by Mason and Raper (Ref. 7, p. 50), explored the pH effect on the sequence of events that characterize the electrooxidation of catecholamines. Thus, the cyclic voltammogram in I M HCIO4 (pH 0.6) shows only peaks corresponding to the catechol-quinone redox couple as the protonation of the amino group prevents the cyclization step. 

The biosynthetic pathway for melanin formation, operating in insects, animals, and plants, has largely been elucidated by Raper [15], Mason [16], and Lerner et al. [17]. The first two steps in the pathway are the hydroxylation of monophenol to o-diphenol (monophenolase or cresolase activity) and the oxidation of diphenol to o-quinones (diphenolase or catecholase activity), both using molecular oxygen followed by a series of nonenzymatic steps resulting in the formation of melanin [15,18,19]. The whole pathway for melanin biosynthesis is shown in Scheme 1. 

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