Eumelanins structure

The oxidative polymerization of 5,6-dihydroxyindole (1) and related tyrosine-derived metabolites is a central, most elusive process in the biosynthesis of eumelanins, which are the characteristic pigments responsible for the dark color of human skin, hair, and eyes. Despite the intense experimental research for more than a century,36 the eumelanin structure remains uncharacterized because of the lack of defined physicochemical properties and the low solubility, which often prevents successful investigations by modem spectroscopic techniques. The starting step of the oxidative process is a one-electron oxidation of 5,6-dihydroxyindole generating the semiquinone 1-SQ (Scheme 2.7). 

Melanins are complex polymeric structures, which are usually mixtures of macromolecules. Melanins are classified as eumelanins, phaeomelanins and allomelanins. ... 

Because of their very complex chemical structures and heterogeneity, melanins are difficult to extract, separate, and characterize from tissues. Eumelanins are insoluble in water and organic solvents. They can be extracted from tissues with strong chemicals that are capable of removing lipids, proteins, and other tissue components but also lead to the formation of degradation products. Enzymatic procedures were developed for the isolation of eumelanins from mammalian hair and irises. The first step is sequential digestion with protease, proteinase K, and papaine in the presence... 

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. 

Melanins are classified according to their chemical structure into the insoluble black eumelanins (poly-5,6-indole quinones) and the alkali-soluble red phaeomelanins (polydihydrobenzothiazines). Nicolaus (5) includes another group, the homoaromatic phenolic allomelanins (per-... 

The subsequent conversion of these intermediates to eumelanins is still far from being well understood and represents a major focus for further work aimed at a definite understanding of the structure of both natural and synthetic melanins. 

The relatively poor solubility of natural and synthetic eumelanins (Table IV) is a considerable obstacle in structural determination. The rate of particle sedimentation in aqueous suspensions of synthetic melanins is... 

The understanding of melanin structure has been attempted via analytical and biosynthetic approaches. The analytical one originally explored by Nicolaus (3,7,310) has led to the development of a number of useful methods for characterizing natural and synthetic melanins in terms of elemental composition, functional groups, and structural features of the pigment backbone. These methods helped in the elucidation of the partial polymeric structure of the eumelanin sepiomelanin (3) seen below. 

The ability of NMR spectrometers to operate in the cross-polarization/ magic angle spinning mode is a powerful tool for structural elucidation of insoluble materials (556). Natural abundance solid-phase C-NMR spectra could be obtained for synthetic L-dopa eumelanin. The inordinate number of resonance signals, however, prevented definitive assignments of the peaks to specific carbons. Subsequently Chedekel et al. (357) used this technique to study the conversion of specifically labeled L-dopa and... 

Although the exact structure of eumelanin has still not been determined, there is strong evidence that it has a polymeric structure built up of 5,6-dihydroxyindole 1, 5,6-indolequinone 6 and semiquinone 7 monomers. Eumelanin has exceptionally good photoprotective properties and an absorption spectrum spanning a large part of the solar spectrum. These special properties have prompted a number of theoretical studies of 5,6-dihydroxyindoles, their oxidation products and dimers, and oligomeric models of eumelanin. 

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]. 

Eumelanins and phaeomelanins are derived from L-tyrosine by tyrosinase (Fig. 289). In the first step tyrosinase hydroxylates L-tyrosine to l-DOPA. In the later steps l-DOPA and other intermediates are dehydrogenated to compounds with o-quinonid structures (C 2.3.1). The indole ring system is formed by... 

DTS 09] DTschia M., Napolitano A., Pezzella A. et al, Chemical and Structural Diversity in Eumelanins Unexplored Bio-Optoelectronic Materials . 

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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