Tyrosine melanin from

Oxidative polymerization of phenol derivatives is also important pathway in vivo, and one example is the formation of melanin from tyrosine catalyzed by the Cu enzyme, tyrosinase. The pathway from tyrosine to melanin is described by Raper (7) and Mason (8) as Scheme 8 the oxygenation of tyrosine to 4-(3,4-dihydro-xyphenyl)-L-alanin (dopa), its subsequent oxidation to dopaqui-none, its oxidative cyclization to dopachrome and succeeding decarboxylation to 5,6-dihydroxyindole, and the oxidative coupling of the products leads to the melanin polymer. The oxidation of dopa to melanin was attempted here by using Cu as the catalyst. 

Both tryptophan and tyrosine fiamished melanin. Similar results were also obtained by Allegri et al. (3), who studied melanin synthesis from tryptophan and tyrosine spectrophotometrically. From tyrosine, p-hydro-xyphenylpyruvic acid (15), 4,4-dihydroxybiphenyl (16), 5,6-dihydroxy-indole (17), and 3,5,6-trihydroxyindole (18) were obtained in addition to melanin and from tryptophan, 5,6-dihydroxyindole (17), indole (19), anthranilic acid (20), 3-hydroxyanthranilic acid (21), indolylpyruvic acid (22), 3-hydroxypyrrol-4,5-dicarboxylic acid (23), and isatin (24). 

In alkaptonuria, homogentisic acid (28) is excreted in excessive amounts indicating that in this metabolic disease the opening of the aromatic ring and complete oxidation to CO2 and H2O is blocked. In albinism, there is a deficiency of the enzyme systems responsible for the formation of melanin from tyrosine (24) (Figure 3.7). 

CgHiiNO. M.p. 282 C (decomp.). The naturally occurring substance is laevorotatory. It is an amino-acid isolated from various plant sources, but not found in the animal body. It is formed from tyrosine as the first stage in the oxidation of tyrosine to melanin. It is used in the treatment of Parkinson s disease. 

Phenoxazines — The two main types of phenoxazines are the ommochromes and the microbial phenoxazines. The biosynthesis of ommochromes occurs via the kynurenine pathway. The tryptophan amino acid is converted to formylkynurenine and then to kynurenine and 3-hydroxykynurenine. Not all the steps of ommochrome synthesis are completely elucidated yet. Ommatins are dimers and ommins are oligomers of 3-hydroxykynurenine. - The papiliochromes are derived from tyrosine as well as from the tryptophan pathway. The key intermediate in the formation of papiliochromes is N-beta-alanyldopamine (NBAD). Papiliochromes are synthesized in special wing scale cells, before melanins. " "... 

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. 

The pathway of melanin synthesis starts from the amino acid tyrosine (Fig. 1). The first two reactions are catalyzed by the copper-containing enzyme tyrosinase (EC 1.14.18.1). Tyrosine is hydroxylated to 3,4-dihy-... 

Figure 1. The biosynthetic pathway from tyrosine to melanin (according to Hearing and Tsukamoto, 1991 Tsukamoto et al., 1992). Tyrosinase catalyzes three different reactions in this pathway (1, 2, 3). The reaction catalyzed by the product of TRP-2, DOPAchrome tautomerase, is indicated by 4. DOPA = 3,4-dihydroxyphenylalanine DHICA = 5,6-dihydroxyin-dole-2-carboxylic acid DHI = 5,6-dihydroxyindole.

In addition to their well known role in protein structure, amino acids also act as precursors to a number of other important biological molecules. For example, the synthesis of haem (see also Section 5.3.1), which occurs in, among other tissues, the liver begins with glycine and succinyl-CoA. The amino acid tyrosine which maybe produced in the liver from metabolism of phenylalanine is the precursor of thyroid hormones, melanin, adrenaline (epinephrine), noradrenaline (norepinephrine) and dopamine. The biosynthesis of some of these signalling molecules is described in Section 4.4. 

Tyrosine (Tyr or Y) (4-hydroxyphenylalanine ((5)-2-amino-3-(4-hydroxyphenyl)-propanoic acid)) is a polar, neutral, aromatic amino acid with the formula H00CCH(NH2)CH2C6H50H and is the precursor of thyroxin, dopamine, norepinephrine (noradrenaline), epinephrine (adrenaline), and the pigment melanin. Being the precursor amino acid for the thyroid gland hormone thyroxin, a defect in this may result in hypothyroidism. Tyr is extremely soluble in water, a property that has proven useful in isolating this amino acid from protein hydrolysates. The occurrence of tyrosine- 0-sulfate as a constituent of human urine and fibrinogen has been reported. ... 

Answer E. The child has PKU aspartame contains phenylalanine. These children may be blond, blue eyed, and pale complected because of deficient melanin production from tyrosine. 

Tyrosine is structurally related to and derived from phenylalanine. It is the metabolic precursor to dopamine, an important neurotransmitter. Tyrosine is also the precursor to the hormones epinephrine and norepinephrine and to melanin, the pigment of skin. 

As the melanin structure grows, it becomes more colored giving various shades of brown color to our skin. This brown coloration acts to help protect deeper skin elements from being damaged by the UV radiation. The absence of the enzyme tyrosinase that converts tyrosine to melanin can lead to albinism. 

In a study of intermediate duration, dermal application of 0.5% p-cresol for 6 weeks produced permanent depigmentation of the skin and hair of mice (Shelley 1974). A caustic effect on the skin was noted in one strain of mouse, but not another. Neither o- nor m-cresol produced any color change in the mice. The author suggests that only p-cresol is active because it mimics the structure of tyrosine, the amino acid present in melanin, so that tyrosinase acts on it, liberating free radicals that damage melanocytes. NOAEL and LOAEL values were not derived from this study because the applied dose was not reported. 

Albinism <3 Melanin synthesis from tyrosine Tyrosine 3-monooxygenase (tyrosinase) Lack of pigmentation white hair, pink skin... 

Albinism refers to a group of conditions in which a defect in tyrosine metabolism results in a deficiency in the production of melanin. These defects result in the partial or full absence of pigment from the skin, hair, and eyes. Albinism appears in different forms, and it may be inherited by one of several modes autosomal recessive, autosomal dominant, or X-linked. Complete albinism (also called tyrosinase-negative oculocutaneous albinism) results from a defi ciency of tyrosinase activity, causing a total absence of pigment from the hair, eyes, and skin (Figure 20.20). It is the most severe form of the condition. Affected people may appear to have white hair, skin, and iris color, and they may have vision defects. They also have photophobia (sunlight is painful to their eyes), they sun burn easily, and do not tan. 

Oxidation of L-DOPA to L-dopaquinone is an important biological process, and dopaquinone is known to play a key role in the oxidative conversion of tyrosine into melanins, the primary pigments of skin and hair. It has been found that under biomimetic conditions both resorcinol and phloroglucinol inhibit this action of L-DOPA, and the compound 1 was isolated from the enzyme-catalysed L-DOPA/phloroglucinol reaction. Compound 1 could also be prepared by fenicyanide oxidation of a mixture of L-DOPA and phloroglucinol. 

Catechol melanin, a black pigment of plants, is a polymeric product formed by the oxidative polymerization of catechol. The formation route of catechol melanin (Eq. 5) is described as follows [33-37] At first, 3-(3, 4 -dihydroxyphe-nyl)-L-alanine (DOPA) is derived from tyrosine. It is oxidized to dopaquinone and forms dopachrome. 5,6-Dihydroxyindole is formed, accompanied by the elimination of C02. The oxidative coupling polymerization produces a melanin polymer whose primary structure contains 4,7-conjugated indole units, which exist as a three-dimensional irregular polymer similar to lignin. Multistep oxidation reactions and coupling reactions in the formation of catechol melanin are catalyzed by a copper enzyme such as tyrosinase. Tyrosinase is an oxidase con-... 

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. 

Very few radicals exist in tissues at rest . Two important exceptions are melanin radicals and tyrosine radicals. The former exist in low concentrations in samples of melanin, which is a high polymer made up of units which include potential semiquinone units. It is reasonable to expect some orf/io-semiquinone formation from such structures. The radicals can be thought of as occluded, being sterically protected by surrounding polymer. So far as we know, they have no special chemical significance. 

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