Melanins, production function

A European patent by Kuno and Matsumoto [43] describes the use of olive plant extract as an effective and stable whitening and antiaging agent. This extract is believed to have strong active oxygen elimination function such that it can eliminate superoxide and hydroxyl radicals and also effectively inhibit melanin production. 

The waste products are partially deposited on the Bruch s membrane (Young, 1987) in the form of drusen. The accumulation of lipofuscin in RPE cells appears detrimental to its function (Flood et al., 1984) and causes photoreceptor death (Dorey et ak, 1989). With age, the number of RPE cells decreases in the central retina, and they become pleomorphic (Dorey et ak, 1989). Other changes are also frequent. They include atrophy, depigmentation, hyperplasia, hypertrophy, and cell migration. The melanin concentration in the RPE cells decreases with age, especially in Caucasians, but also in blacks (Feeney-Burns et al., 1984). The melanin granules are slowly (over decades) digested by lysosomes (Bums and Feeney-Burns 1980). 

Because of cataract development and lenticular changes in animals, baseline and periodic eye exams are recommended in the product labeling for patients receiving quetiapine. However, clinical experience with quetiapine since marketing has not supported a significant risk of cataracts. Retinitis pigmentosa can result from use of thioridazine doses greater than 800 mg daily. It is caused by melanin deposits, and can result in permanent visual impairment or blindness. There is no evidence that it is a function of cumulative dose. ... 

Indeed, the biosynthesis of the biopolymer melanin involves the oxidative cyclization of dihydroxyphenylala-nine (DOPA) to phenylalanine-3,4-quinone (dopaquinone), which eventnally forms 5,6-dihydroxyindole (DHI). Polymerization of DHI affords melanin [1], Lim and Patil have exploited this biochemical transformation using commercial mushroom tyrosinase in a synthesis of 5,6-dihydroxyindoles protected as the diacetates (2) (Scheme 1) [2], The parent indole (R = R =H) is obtained in less than 10% yield. Carpender has reported a similar oxidative cyclization using manganese dioxide to give 2 (R =Me) in 80% overall yield from epinine (1, R =Me, R =H) [3]. Other oxidants (H, Hp /FeSO, O, NaOCl, NaClOj/ VjOj) gave little or no product. Choi, Nam, and colleagues have effected an electrochemical oxidation of dopamine (1, R = R =H) to 5,6-dihydroxyindole that polymerizes to form films of polydopamine suitable for neural attachment and function [4]. 

Tyrosiaase occurs in lower animals, especially meal-worms, in many plants, notably clover, potato, and higher fungi. It catalyses the oxidation of the amino acid tyrosine with the production of a red pigment which turns black and becomes insoluble, in which condition it is called melanin. Tyrosinase is believed to function in the formation of natural pigments from tyrosine, and also in the metabolism of the amino acid in lower organisms. 

Phenolase Complex. Phenolase (= tyrosinase, or phenol oxidase) converts tyrosine to dopa (= dihydroxyphenylalanine) and oxidizes the dihydroxy derivative further to the quinone stage. Through a series of subsequent reactions, some of which occur spontaneously and wathout enzymic catalysis, the black or brownish black melanin is finally formed (for a schematic representation of the reactions see Chapt. VIII-11). The phenolase is an oxidase with mixed functions, where the product of oxygenation, the hydroquinone derivative, simultaneously acts as... 

Copper is present in a number of mammalian proteins and the characteristics of these have been summarized by Scheinberg and Sternlieb [3]. Amongst the copper proteins identified in man, but of unknown function, are cerebro-cuprein I, a protein extracted from normal human brain by Porter and Ainsworth [4], liver copper-protein [5], and erythrocuprein [6]. Tyrosinase, a protein of 0.25% copper content is to be found wherever melanin is present in the body, it catalyses the oxidation of tyrosine to dopa and accelerates the conversion of dopa to dopa quinone, the initicJ stages in the conversion of tyrosine to melanin. Lack of this enzyme is not, however, associated with deficient production of pressor amines, another pathway being present in the adreneil gletnd for the hydroxylation of tyrosine [7]. 

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