Synthesis of Melanin

Synthetic melanins are obtained by biomimetic oxidation reactions using known precursors. So far, four different methods for melanin synthesis have been reported, i.e. in vitro enzymatic, autooxidative, electrochemical, and photochemical methods. Of these, the first two have been generally used, for large scale preparations of the pigment polymers and have been reviewed elsewhere (70, 211). The latter two methods which are discussed here, have been used effectively to understand the mechanism of the melanization process in biological systems. 

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The anterior lobe secretes various trophic hormones, the posterior lobe is responsible for the secretion of oxytocin and antidiuretic hormone (vasopressin) and middle lobe secretes melanocyte-stimulating hormone (MSH) which may affect the synthesis of melanin. 

Various stimuli, including ultraviolet irradiation of melanocytes, cause increased synthesis of melanin with a resultant tanning0 and added protection against sunburn. 

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. 

Melanin Synthesis. Tyrosinase is a copper-containing enzyme that is present in melanocytes and catalyzes the synthesis of melanin. Starting with L-dopa as a substrate, tyrosi-... 

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. 

The stratum corneum is a 10-20 pun thick non-viable epidermis, consisting of 15 to 25 flattened and stacked cornified cells. Each stratum corneum cell is composed mainly of insoluble bundled keratins (—70 percent) and lipids ( 20 percent) encased in a cell envelope. The intercellular region consists mainly of lipids together with desmosomes which provide cor-neocyte cohesion, as described later. There is continuous desquamation of the outermost layer of the stratum corneum, with a total turnover occurring once every two to three weeks. The most important function of the viable epidermis is the generation of the stratum corneum, which is described in detail below. Other functions include metabolism and the synthesis of melanin from melanocytes for skin pigmentation and sun protection. 

The RPE of the eye is a monolayer membrane located between the photoreceptors and the chorioid (Fig. 14.2), and it is thought to function as a support tissue for the photoreceptors. hRPE cells are involved in retinoid transport, esterification and isomerization processes, and the phagocytosis and degradation of shed outer segments. It participates in the regulation of ion channels and the extravasation of metabohtes, and - depending on the developmental state of the individual - synthesis of melanin. 

The fundamental work of Raper 216) on the in vitro enzymatic synthesis of melanin, using tyrosinase, tyrosine and oxygen, was the first synthetic approach investigating melanogenesis and the structure of... 

Catecholamines are thermodynamically and photochemically unstable compounds. This property has been utilized in the photochemical synthesis of melanin (74, 277). Thus, a dilute solution of adrenaline, iso-prenaline and noradrenaline saturated with oxygen on irradiation (254 nm) gives the corresponding aminochromes in 65, 56, and 35% yield, respectively. Longer irradiation produces melanins (74). Studies of the action spectrum confirmed the excited state of the catecholamine as the primary factor in the transformation processes. N-suhstituted catecholamines have been found to react more rapidly than the corresponding N-unsubstituted ones (74). 

Fig. 8. Combined tyrosine and tryptophan participation for the synthesis of melanin and its catabolism in relation to vitiligo (modification of...

Classical tyrosinase (catechol oxygenase, EC 1.10.3.1) catalyses the first step in the synthesis of Melanin (see) from tyrosine. 

The only known inborn error of metabolism that can be linked to a copper-dependent enzyme is albinism, A genetically acquired absence of the enzyme tyrosinase results in albinism, which is characterized by the complete lack of pigmentation in the eyes and integument. Tyrosinase is essential in the pigmentation process because this enzyme catalyzes the first two steps in the synthesis of melanin pigment from tyrosine. Mammals that lack pigment do not have the capability to filter the sun s ultraviolet rays, which penetrate the integument and cause molecular havoc. 

Bearberry Arctostaphylos uva-ursi (L.) Spreng is a small shrub, whose leaves contain arbutin, a hydroquinone heteroside, that yields hydroquinone after degradation by a j3-glucosidase enzyme. Hydroquinone acts by inhibiting the tyrosinase enzyme, which initiates the biochemical synthesis of melanin. At present, the use of this hydroquinone glucoside is becoming less and less frequent because of the restrictions on the use of synthetic hydroquinones for cosmetic applications and because of its well-known irritant effects on the skin (Maeda and Fukuda, 1991, 1996). 

Tyrosinase catalyzes the synthesis of melanin through the hydoxylation of tyrosine to dihydoxyphenylalanine (DOPA) and the subsequent oxidation of DOPA to dopaquinone. The unstable dopaquinone will polymerize and precipitate into melanin. However, in the presence of a reductor, the reaction will stop at the dlphenol level [2]. The cresolase activity of tyrosinase is of particular importance because it synthesizes DOPA. DOPA is a precursor of dopamine, an important neural message transmitter. 

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