Biosynthesis of melanin

Polyphenoloxidase (PPO, EC 1.14.18.1) is one of the most studied oxidative enzymes because it is involved in the biosynthesis of melanins in animals and in the browning of plants. The enzyme seems to be almost universally distributed in animals, plants, fungi, and bacteria (Sanchez-Ferrer and others 1995) and catalyzes two different reactions in which molecular oxygen is involved the o-hydroxylation of monophenols to o-diphenols (monophenolase activity) and the subsequent oxidation of 0-diphenols to o-quinones (diphenolase activity). Several studies have reported that this enzyme is involved in the degradation of natural phenols with complex structures, such as anthocyanins in strawberries and flavanols present in tea leaves. Several polyphenols... 

The mechanism of action of these compounds appears to involve inhibition of the enzyme tyrosinase, thus interfering with the biosynthesis of melanin. In addition, monobenzone may be toxic to melanocytes, resulting in permanent loss of these cells. Some percutaneous absorption of these compounds takes place, because monobenzone may cause hypopigmentation at sites distant from the area of application. Both hydroquinone and monobenzone may cause local irritation. Allergic sensitization to these compounds can occur. Prescription combinations of hydroquinone, fluocinolone... 

Melanin is a collective term for brown or black pigments. They are condensates of phenolics and are widely distributed in nature, examples of this diverse chemistry being found in animals, plants and fungi. They perform various roles but in some fungi, notably Pyricularia oryzae and Colletotrichum spp., melanin biosynthesis is an essential feature in pathogenicity, the biosynthesis of melanin in appressorial walls being a requirement for the development of infection hyphae and subsequent penetration of the host epidermis. For example, melanin-deficient mutants of P. oryzae are not pathogenic. 

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 ... 

Volume 89 of Advance in Heterocyclic Chemistry consists of four chapters. The volume commences with an overview of 5,6-dihydroxyindoles and the corresponding diones authored by M. DTschia, A. Napolitano and A. Pezzella (University of Naples, Italy), E. J. Land and C. A. Ramsden (Keele University, UK) and P. A. Riley (Mount Vernon Hospital, UK). These compounds play essential roles in the biosynthesis of melanins, the ubiquitous pigments of hair and many other body parts of all mammals including humankind. 

According to Pawelek et al. 200), the biosynthesis of melanin in Cloudman melanoma cells is a complex process and is regulated by three factors (a) a dopamine conversion factor which converts dopamine to 5,6-dihydroxyindole (13), (b) a 5,6-dihydroxyindole conversion factor which catalyzes the conversion of 5,6-dihydroxyindole to melanin and is active when cells are exposed to melanotropin (MSH), and (c) a 5,6-dihydroxyindole blocking factor which restricts melanogenesis at the 5,6-dihydroxyindole stage. They have also shown that at least three steps in the Raper-Mason scheme of melanin formation from tyrosine are catalysed by tyrosinase (Fig. 6). 

For many years the biosynthesis of melanin was thought to result from the spontaneous oxidation and polymerization of dopachrome produced by the tyrosinase-catalyzed hydroxylation of tyrosine to dopa and subsequent oxidation (5 ). In addition to tyrosinase, however, several enzymatic factors have been recently identified in mammalian tissues that appear to regulate melanogenesis at intermediate steps distal to those involving tyrosine and dopa. The factors include dopachrome conversion factor, dihydroxyindole blocking factor, dihydroxyindole conversion factor and dopachrome oxidoreductase (54-59). 

Tyrosinase. Tyrosinase is a very well-studied multicopper oxygenase, which contains a magnetically coupled dinuclear copper center. This enzyme catalyzes the ortho-hydroxylation of phenols to catechols (phenolase activity, also called cresolase activity), as well as the 2-electron oxidation of catechols to 0-quinones (catecholase activity), which is the initial step for the biosynthesis of melanin (Scheme 1) (7,13). 

Swan, G. A. Structure, Chemistry and Biosynthesis of Melanins. Prog. Chem Org. Nat. Prod. 32, 521-582(1974)... 

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