Melanins pheomelanins

Keywords— skin chromophores, melanin, pheomelanin, eumelanin, modified Beer-Lambert law. 

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...

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. 

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. 

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. 

Ty initiates melanin synthesis by the hydroxylation of L-tyrosine to 3,4-dihydroxyphenylalanine (Dopa) and the oxidation of dopa to dopaquinone. In the presence of L-cysteine, dopaquinone rapidly combines with the thiol group to form cysteinyldopas, which undergo nonen-zymatic conversion and polymerization to pheomelanin via benzothiazine intermediates. In the absence of thiol groups, dopaquinone very rapidly undergoes conversion to dopachrome, which is transformed to 5,6-dihydroxyindole-2-carboxylic acid (DHICA) by dopachrome tautomerase. Alternatively, dopachrome is converted nonenzymatically to 5,6-dihydroxyindole (DHI). Oxidation of DHICA and DHI to the corresponding quinones and subsequent polymerization leads to eumelanins. It is still questionable if Ty is involved in this step. 

The natural colour of animal fibre is closely related to the character of environment in which the animal lives [19]. Wool lots completely free of dark fibres do not exist [20]. In animal (and human) hair two kinds of pigments occur, namely eumelanin (responsible for black, dark brown and grey colours and commonly referred to as melanin) and pheomelanin (present in yellow, reddish-brown and red hair). Both are thought to be formed by different mechanisms and chemically differed [21]. Eumelanin is formed by enzymatic (tyrosinase) oxidation of tyrosine and polymerisation of several oxidation product [22]. Pheomelanin occurs in form of discrete grannules. Melanin grannules can occur in the cortex or in the cuticle. 

The first two steps in the synthesis of melanin are catalyzed by tyrosinase, a copper-containing oxidase, which converts tyrosine to dopaquinone. All subsequent reactions presumably occur through nonenzymatic auto-oxidation, in the presence of zinc, with formation of the black to brown pigment eumelanin. The yellow to reddish brown, high-molecular-weight polymer known as pheomelanin and the low-molecular-weight trichromes result from addition of cysteine to dopaquinone and further modification of the products. Pheome-lanins and trichromes are primarily present in hair and feathers. 

ESR spectra of melanins are fairly characteristic. Eumelanins (derived mostly from dopa), which are the most common, show a single line with a g value close to 2.004 and a linewidth of approximately 4 G (Fig. 10a) [68]. Pheomelanins (from cysteinyldopa) have a quite different spectrum (Fig. 10b) which shows evidence of hyperfine interaction with nitrogen [164]. Many natural melanins are evidently derived from mixtures of dopa and cysteinyldopa and show intermediate spectra (Fig. 10c). 

Figure 10. ESR spectra ( — 196°C) from different forms of melanin, a. Melanin from oxidation of dopa (a eumelanin) b, melanin from oxidation of cysteinyldopa (a pheomelanin) c, melanin from cooxidation of dopa and cysteinyldopa. From [164], with permission.

From a chemical point of view, and in a very simplified way, in the animal kingdom the so-called eumelanins (or melanins tout-court), black or dark brown, and completely insoluble in water, differ from pheomelanins, that contain sulfur, varying from yellow to brown-red, and alkali-soluble. Both the kinds of melanin can be present at the same time within the same organism. For a deeper insight in melanin occurrence and properties, see [238],... 

The presence of phenoloxidase in all phyla of living organisms demonstrates that their origin is very early in the history of life. It is involved in the biosynthesis of melanins and other polyphenolic compounds. Depending on the species, phenoloxidases are involved in the primary immune response, wound healing, sclerotization, and coloring processes. 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 pheo-and eumelanins.Ti ... 

The principal pigments of human hair are the brown-black melanins (eume-lanins) and the less prevalent red pigments (pheomelanins). These latter pigments at one time were called trichosiderins. For this discussion, the brown-black pigments of hair will be referred to as melanins, and the yellow and red pigments will be referred to as pheomelanins. 

Pheomelanins are the yellow-red pigments and are lighter in color than the brown-black pigments of human hair. Both pheomelanins and eumelanins occur as granules in melanocytes. Prota and co-workers [14,62] have proposed that red hair pigments are formed by a modihcation of the eume-lanin pathway described earlier. The pheomelanin pathway, however, involves the interaction of cysteine with dopaquinone. Figure 4-28 summarizes Prota s [62] description of a common metabolic pathway for formation of all melanins and shows how pheomelanin formation relates to eumelanin biosynthesis. 

The two melanins are formed from a common metabohc pathway that involves highly reactive intermediates. It is highly probable, therefore, that both types of pigments (eumelanin and pheomelanin), and even mixtures of these two pigments and the trichochromes, may be formed in the same hair, depending primarily on the amount of cysteine present in the melanocyte. Wolfram and Albrecht [65] have also shown that hue differences in hair not only result from chemically different pigments but also... 

Both eumelanins and pheomelanins are polymeric and are believed to be formed from a common metabohe pathway. Both of these polymeric pigments contain polypeptide chains with similar amino acids [66]. The red hair melanin contains more sulfur (as 1,4-benzothiazine units) than the brown-black melanins. 

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. 

Melanin is produeed by melanocytes. Melanin has different two components namely, pheomelanin (reddish skin appearance) and eumelanin (brownish skin appearance) [Diffey, 1983]. Eumelanin is more abundant in people with dark skin. Pheomelanin is found in both light and dark... 

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. 

Experiment performed by Vincensi et al (Vincensi, 1998) indicated that increasing skin pigment (SPT I to Vt) correlates with changes in pheomelanin/melanin production ratios among SPT. Lower SPT will have higher pheomelanin and lower eumelanin production ratio. 

In this paper, we have developed a skin pigmentation model for melanin pigment (eumelanin /pheomelanin) analysis. The proposed model is based on modified Beer-Lambert law of skin reflectance model. Clinical study involving 118 participants with three different skin phototypes (SPTs) is conducted. In the study, it was found that the pheomelanin concentration is -4.6E5 5.4E-6 moles/1 for SPT III, -5.9E-5 6.4E-6 moles/1 for SPT IV, and -8.2E-5 9.8E-6 moles/1 for SPT V) and the eumelanin concentration is 9.7E-5 7.3E-6... 

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