Pheomelanins structure

Enzymes present in melanosomes synthesize two types of melanin, eumelanin and pheomelanin. Figure 2 illustrates the proposed biosynthetic pathways of eumelanin and pheomelanin. The synthesis of eumelanin requires tyrosinase, an enzyme located in melanosomes. Tyrosinase catalyzes the conversion of tyrosine to dopa, which is further oxidized to dopaquinone. Through a series of enzymatic and nonenzymatic reactions, dopaquinone is converted to 5,6-indole quinone and then to eumelanin, a polymer. This polymer is always found attached to proteins in mammalian tissues, although the specific linkage site between proteins and polymers is unknown. Polymers affixed to protein constitute eumelanin, but the exact molecular structure of this complex has not been elucidated. Pheomelanin is also synthesized in melanosomes. The initial steps in pheomelanin synthesis parallel eumelanin synthesis, since tyrosinase and tyrosine are required to produce dopaquinone. Dopaquinone then combines with cysteine to form cysteinyldopa, which is oxidized and polymerized to pheomelanin. The exact molecular structure of pheomelanin also has not been determined. 

Although the structures of pheomelanin and eumelanin have not been resolved, melanin is one of several suspected binding sites in hair for metals, chemicals, and drugs of abuse. The quantity and type of melanin in hair should determine the extent to which drugs bind to hair. Melanin is present in several mammalian tissues including the brain, skin, hair, iris of the eye, vas deferens, and cochlea of the inner ear. - Since melanin is present in many human tissues, drug may bind to other bodily tissues as well as hair. 

Cyclization and oxidative polymerization of 5-S-cysteinyldopa and its isomers (present in smaller quantities) forms the high-molecular-weight yellow-red pheomelanins. A partial structure, proposed by Prota [62], for pheomelanins, is depicted in Figure 4-29. 

Figure 4-29. Partial structure proposed by Prota for the primary unit of pheomelanins.

Monophenol oxidase catalyzes the hydroxylation of monophenols to o-diphenols (Figure 11.1). The enzyme is referred to as tyrosinase in animals, since L-tyrosine is the major monophenolic substrate [37], In mammals, L-tyrosine is the initial substrate in the pathway leading to the final products of black-brown eumelanins, red-yellow pheomelanins, or a mixture of pheomelanins and eumelanins. In plants, the enzyme is sometimes referred to as cresolase owing to the ability of the enzyme to utilize the monophenolic substrate, cresol. In microorganisms and plants, a large number of structurally different monophenols, diphenols, and polyphenols serve as substrates for tyrosinase. As many plants are rich in polyphenols, the name PPO has been frequently used for this enzyme [38]. 

The chemical degradation of both eu- and pheomelanin has been studied, mainly by three methods. Although the yield of products in most experiments is very low and varies significantly for melanins of different origin, the results appear particularly useful in leading to an understanding of the monomeric units present in the pigment structure. 

In general the above methods can be used to characterise the structure and properties of skin. However they do not classify nor measure in detail the types of melanin (eumelanin and pheomelanin) which is important in understanding the underlying causes of skin pigmentation disorder. In this research, the spectral reflectance of human skin will be applied to a proposed pigmentation model in order to analyse and measure the melanin content (pheomelanin and eumelanin) for use in clinical assessment of skin pigmenation disorders. 

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