Dopamine-melanin

Double, K.L. et al., Structural characteristics of human substantia nigra neuromelanin and synthetic dopamine melanins, J. Neurochem., 75, 2583, 2000. 

Tyrosine Adrenaline Noradrenaline Dopamine Melanin, thyroxine... 

Skin pigmentation Dopamine-melanin conversion All less potent neuroleptics... 

Presence of less uncyclized side chains than dopamine-melanin 213... 

Natural black (human hair, bovine eyes) and synthetic (tyrosine, dopa, and dopamine) melanins were investigated by Curie point pyrolysis-gas chromatography-mass spectrometry (86,96). The pigments were characterized by different ratios of degradation products identified as aromatic hydrocarbons, phenols, catechols, pyrroles, and indoles. The amount of ash in karakul lamb wool was correlated to its color, with black producing the most (3.9%) and white the least (1.2%). Similar studies showed a correlation with the calcium content (317,318). 

Vibrational band p (cm" ) L-Dopa melanin Dopamine melanin Sepia melanin Eye melanin ... 

Manganese has been found to have an affinity for melanin (it was found to bind to beef eye, human hair, and synthetic dopamine melanin) although functional damage has not been reported (Lyd6n et al. 

Natural black (human hair, bovine eyes) and synthetic tyrosine-, dopa-, dopamine-melanins were investigated by Curie point pyrolysis-... 

Neural cells convert tyrosine to epinephrine and norepinephrine (Figure 31—5). While dopa is also an intermediate in the formation of melanin, different enzymes hydroxylate tyrosine in melanocytes. Dopa decarboxylase, a pyridoxai phosphate-dependent enzyme, forms dopamine. Subsequent hydroxylation by dopamine P-oxidase then forms norepinephrine. In the adrenal medulla, phenylethanolamine-A -methyltransferase uti-hzes S-adenosyhnethionine to methylate the primary amine of norepinephrine, forming epinephrine (Figure 31-5). Tyrosine is also a precursor of triiodothyronine and thyroxine (Chapter 42). 

Copper is part of several essential enzymes including tyrosinase (melanin production), dopamine beta-hydroxylase (catecholamine production), copper-zinc superoxide dismutase (free radical detoxification), and cytochrome oxidase and ceruloplasmin (iron conversion) (Aaseth and Norseth 1986). All terrestrial animals contain copper as a constituent of cytochrome c oxidase, monophenol oxidase, plasma monoamine oxidase, and copper protein complexes (Schroeder et al. 1966). Excess copper causes a variety of toxic effects, including altered permeability of cellular membranes. The primary target for free cupric ions in the cellular membranes are thiol groups that reduce cupric (Cu+2) to cuprous (Cu+1) upon simultaneous oxidation to disulfides in the membrane. Cuprous ions are reoxidized to Cu+2 in the presence of molecular oxygen molecular oxygen is thereby converted to the toxic superoxide radical O2, which induces lipoperoxidation (Aaseth and Norseth 1986). 

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. 

Costa C, Bertazzo A, Allegri G, Toffano G, Curcuruto O, et al. 1992. Melanin biosynthesis from dopamine. II. A mass spectrometric and collisional spectroscopic investigation. Pigment Cell Res 5 122. 

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. ... 

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. 

Copper is a component of many enzymes including amine oxidase, lysyl oxidase, ferroxidase, cytochrome oxidase, dopamine P-hydroxylase, superoxide dismutase and tyrosinase. This latter enzyme is present in melanocytes and is important in formation of melanin controlling the colour of skin, hair and eyes. Deficiency of tyrosinase in skin leads to albinism. Cu " ion plays an important role in collagen formation. 

Dihydroxyindole and 5,6-dihydroxyindole-2-carboxylic acid were shown to form after the red pigment stage that occurred during the conversion of DOPA into a melanin, by Raper, who isolated these compounds as their dimethyl ethers.72 The presence of 5,6-dihydroxyindoles in solutions of DOPA, dopamine, and noradrenaline which are undergoing oxidation has subsequently been confirmed by paper and thin-layer chromatography.118,120,222 5,6-Dihydroxyin-dole and 5,6-dihydroxyindole-2-carboxylic acid have recently been isolated from the alkali fusion products of sepiomelanin, indicating... 

A combination of decarboxylation and hydroxyla-tion of the ring of tyrosine produces derivatives of o-dihydroxybenzene (catechol), which play important roles as neurotransmitters and are also precursors to melanin, the black pigment of skin and hair. Catecholamines may be formed by decarboxylation of tyrosine into tyramine (step e, Fig. 25-5) and subsequent oxidation. However, the quantitatively more important route is hydroxylation by the reduced pterin-dependent tyrosine hydroxylase (Chapter 18) to 3,4-dihydroxyphenylalanine, better known as dopa. The latter is decarboxylated to dopamine.1313 Hydroxylation of dopamine by an ascorbic acid and... 

With branched catechols carrying nucleophilic groups in the side chains, the ring closure reaction occurs. Typical examples are the peroxidase oxidation of dopa and dopamine, which produce a series of compounds such as dopachrome and dopami-nechrome, respectively, which further evolve to compounds related to melanin pigments [46] (Fig. 6.3c). 

Besides these enzyme substrates, a number of biological molecules are likely to give rise to fairly stable and hence observable free radicals. The more important of these are the quinonoid molecules, particularly vitamin Q quinone (ubiquinone), vitamin E quinone, vitamins K, Ks and vitamin E quinone, the flavins and flavoproteins and the important neurochemicals dopa, dopamine, and closely related phenolic and quinonoid molecules. In many of these cases, the generation of free radicals from these molecules should occur in vivo, but as yet only a few radicals such as the ascorbyl radical and the bacteriochlorophyll radical have been directly identified in intact systems. Free radicals from melanins (polymers from dopaquinone) have been demonstrated both in vivo and in vitro, but these radicals are so stable that it has not yet been possible to identify a biological role for the radicals per se. 

The authors speculated that the increased concentrations of dopamine may have interfered with melanin synthesis. 

Thyroid hormone, 3,4-dihydroxy phenylalanine (dopa), melanin, dopamine, norepinephrine, and epinephrine are produced from tyrosine. 

C. Tetrahydrobiopterin is involved in hydroxylation reactions that occur in phenylalanine to tyrosine, tyrosine to dopamine, and tryptophan to serotonin, but not in the conversion of dopa to melanin. 

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