Eumelanins

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

Eumelanins — These melanins are considered polymers derived from tyrosine derivatives, mainly 5,6-dihydroxyindole-2-carboxylic acid (DHCIA) and dihidrox-yindole (DHl), with high degrees of cross-linking. In vivo eumelanins are associated with proteins and with metals, most frequently copper, zinc, or iron. 

Melanins are prodnced in mammals in two types of cells of different developmental origin (1) the melanocytes of the skin, hair, choroids and iris and (2) the retinal pigment epithelium (RPE). Specialized organelles of the melanocytes, the melano-somes, synthesize and store eumelanins and phaeomelanins. 

Melanin biosynthesis in animals is a complex process starting with the L-tyrosine amino acid. In the first step, L-tyrosine is converted first into DOPA and then into dopaquinone, a process catalyzed by tyrosinase. In the biosynthesis of eumelanins, dopaquinone undergoes a cyclization to form dopachrome and subsequently a tau-tomerization into 5,6-dihydroxyindole-2-carboxylic acid (DHICA). DHICA is further oxidized to indole-5,6-quinone2-carboxylic acid, the precnrsor of DHICA eumelanins. Tyrosinase-related proteins TRP-2 and TRP-1, respectively, are responsible for the last two steps, and they are under the control of the tyrosinase promoter. 

Dopachrome also undergoes a nonenzymatic reaction to form dihidroxyindole (DHI), the precursor of DHI-eumelanins. For the formation of phaeomelanins, dopaquinone is first transformed in cysteinil-DOPA and then in cysteinyl-dopaquinone which suffers a nonenzymatic polymerization. The polymerization of monomers and the association of melanins with proteins is not yet completely elucidated and may involve other intermediates. ... 

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... 

Novellino, L., Napolitano, A., and Fhota, G., Isolation and characterization of mammalian eumelanins from hair and irides, Biochim. Biophys. Acta, 1475, 295, 2000. Capozzi, V. et al., Optical and photoelectronic properties of melanin, Thin Solid Films, 511, 362, 2006. 

Geremia, E.C., Corsano, C., Bonomo, R., Giardinelli, R., Vanella, A. and Sichel, G. (1984). Eumelanins as free radical traps and superoxide dismutase activities in amphibia. Comp. Biochcm. Physiol. 79B, 67-69. 

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). 

Pezzella, A. Panzella, L. Crescenzi, O. Napolitano, A. Navaratman, S. Edge, R. Land, E. J. Barone, V. d lschia, M. Short-lived quinonoid species from 5,6-dihydroxyindole dimers en route to eumelanin polymers integrated chemical, pulse radiolytic, and quantum mechanical investigation. J. Am. Chem. Soc. 2006, 128, 15490-15498. 

Il ichev, Y. V. Simon, J. D. Building blocks of eumelanin relative stability and excitation energies of tautomers of 5,6-dihydroxyindole and 5,6-indolequinone. J. Phys. Chem. B 2003, 107, 7162-7171. 

Melanin from natural sources falls into two general classes. The first component is pheomelanin (I), which has a yellow-to-reddish brown colour, and is found in red feathers and red hair. The other component is eumelanin (which has two principal components, II and III). Eumelanin is a dark brown-black compound, and is found in skin, hair, eyes, and some internal membranes, and in the feathers of birds and scales of fish. Melanin is particularly conspicuous in the black dermal melanocytes (pigment cells) of dark-skinned peoples and in dark hair and is conspicuous in the freckles, and moles of people with lighter skins. 

Figure 9.7 UV-visible spectrum of the skin pigment melanin. The spectrum contains two traces (a) eumelanin and (b) pheomelanin. Both component compounds protect the skin by absorbing harmful UV light. All pigment concentrations were 1 mgdm 3...

Figure 25-6 Postulated pathways for synthesis of the black pigment melanin and pigments (phaeomelanins) of reddish hair and feathers. Dopachrome reacts in two ways, with and without decarboxylation. The pathway without decarboxylation is indicated by green arrows. To the extent that this pathway is followed the green carboxylate groups will remain in the polymer. The black eumelanin is formed by reactions at the left and center while the reddish phaeomelanin is derived from polymers with cysteine incorporated by reactions at the right.

Melanin granules are secreted by melanocytes in the hair papilla and distributed to keratin in the hair cortex and inner layers of the hair sheath during normal development. Melanogenesis is subject to hormonal control and has been the focus of intensive genetic studies. Two main forms of melanin exist in human skin—eumelanin and phaeomelanin, both of which are derived from tyrosine through the action of tyrosinase (a cupro-enzyme) and possibly other key enzymes (with nickel, chromium, iron, and manganese as cofactors). Tyrosine is converted to dihydroxyphenylalanine and, via a series of intermediate steps, to indole-5,6-quinone, which polymerizes to eumelanin. Phaeomelanins are produced by a similar mechanism but with the incorporation of sulfur (as cysteine) by a nonenzymatic step in the oxidation process. 

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. 

There are distinct chemical properties of eumelanin and pheomelanin which affect the physiochemical properties of hair. - Pheomelanin granules are smaller and less resistant to chemical degradation than eumelanin granules. Pheomelanin is soluble in dilute alkali in comparison to eumelanin, which is insoluble in almost all solvents. Pheomelanin and eumelanin also differ in sulfur content. Pheomelanin is high in sulfur content (9 to 12%) in contrast to eumelanin, which contains only 0 to 1% sulfur. ... 

Melanin Varies with hair color (blond, eumelanin (+) brown, eumelanin (++) red, pheomelanin (++) and eumelanin (+) Eumelanin (+++) Eumelanin (+++) ... 

Blond hair contains elliptical and oval melanosomes. The granules in melanosomes are small, few in number, and likely represent eumelanin, although pheomelanin also may be present in blond hair. T22,24 Ortonne and Prota suggested that blond hair results from a quantitative decrease in the synthesis of melanin in comparison to black and brown hair. The main features which distinguish brown hair from blond hair are the presence of more melanosomes and a higher concentration of melanin in brown hair. - Melanosomes present in the shaft of blond hair also appear to be more susceptible to degradation than melanosomes in black hair. Cesarini reported that melanosomes may not be present in the shaft of blond hair, possibly due to digestion of melanosomes by lysosomes. 

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