A pulse radiolysis investigation of the oxidation of the melanin precursors 3,4-dihydroxyphenylalanine (dopa) and the cysteinyldopas (original) (raw)
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… et Biophysica Acta (BBA …, 1989
The rate constants associated with the series of successive transient absorptions initiated by one-electron oxidation of 5,6-dihydroxyindole (DH]), 5,6-dihydroxyindole.2-carboxylic acid (DHICA), precursors of melanin, and N-methyl-5,6dihydroxyindole (NMDHI), a model compound, have been studied by pulse radiolysis. The initial transient species resulting from N~ oxidation reaction at pH 7.3-7.4 are assigned as the corresponding semiquinones. In each case, these radicals decayed, prob~bly by disproportionation, into products most readily monitored in the 400-430 nm region. For Dill, the decay in this region could be fitted by two parent concentration independent first-order processes. "[laese may correspond to transformations between 5,6-indolequinone, and its quinone-imine and quinone-meth~de tautomers. With NMDHI, on the other hand, a single longer-lived product with a peak around 430 nm predominated after decay of the corresponding radical, due almost certainly to N-methyl-5,6-indolequinone. The data appear to exclude significant melanin polymerisation by condensation of semiquinones, reaction of semiquinones ~'ith dihydroxyindoles, self-addition of indolequ~nones or tautomers, or reaction of indolequinones or tautomers with the parent dihydroxyindoles. It is suggested that po|ymerisation of melanin may rather occur by stepwise addition of indolequinone methide/imine to reduced ol~gomeric species.
Biochimica et Biophysica …, 1990
The rate constants associated with the series of successive transient absorptions initiated by one-electron oxidation of 6-hydroxy-5-methoxyindole (6H5MI) and its isomer 5-hydroxy-6-methoxyindole (SH6MI) have been studied by pulse radiolysis. These close analogues of 5,6-dihydroxyindole (DIED are metabolites of the oxidative melanogenic pathway. The species initially produced from N~ oxidation of both methoxyindoles at pH 7.2-7.4 are assigned as the corresponding semiquinones. That from 6H5MI shows peaks at 500, 370 and 330 nm, very close to those of the semiquinone of Dill, whereas the semiquinone of 5H6MI shows no absorption at 500 nm but bands at 420 and 340 nm. These spectral differences are attributed to marked changes in the degrees of electron delocalisation for the two types of radical, both rings of the indole being involved for the 6H5MI radical but only the benzenoid moiety for the 5H6MI radical. In both cases, the radicals decayed, probably by disproportionation, into products which absorbed in the 400-420 nm region. For 6H5MI, the subsequent decay in this region was best fitted by two consecutive first-order processes which were both strongly base-catalysed. The first of these processes is assigned to partial decay via deprotonation of the corresponding quinonoid cation to form an equilibrium mixture of this cation and the corresponding qnlnone methide. The second process is assigned to reaction of the quinone methide with water yielding hydroxylated product(s) which may subsequently react with remaining quinonoid cation or quinone methide to give dimeric product(s) with broad absorption centreing in the 550 nm region detected 0.5 s after the pulse. For 5H6MI, the decay at 430 um fitted a single first-order process, which was weakly base-catalysed. This process is attributed to deprotonation of the corresponding quinonoid cation to the corresponding quinone imine absorbing below 350 nm, which was stable for at least tens of seconds. The current experiments suggest that our previous analogous observations (Lambert et al. (1989) Biochim. Biophys. Acta 993, 12-20) on the oxidation of the melanogenic precursors DHI and 5,6-dihydroxyindole-2-carboxylic acid 0DHICA) may be interpreted, as with 6H5MI, in terms of the corresponding indolequinones decaying into equilibrium mixtures of quinone, quinone imine and quinone methide. These decay via reaction of the methide with water generating hydroxylated species which proceed to give the coloured product(s) absorbing in the 550 nm region.
Optics and Spectroscopy, 2005
The effect of DOPA melanin on the spectral and kinetic properties of the photosensitizers chlorin e 6 and Photolon in buffer solutions with different pH (8.5, 7.0, and 6.0) is studied. The data obtained indicate that no complex formation between molecules of DOPA melanin and either photosensitizer in the ground or excited states occurs (at least, at melanin concentrations ≤ 0.1 mg/ml). The presence of melanin in the samples has no effect on the spectral-luminescent or kinetic characteristics of either chlorin e 6 or Photolon. At a small concentration of DOPA melanin ( ≤ 0.02 mg/ml), the quantum yield of generation of singlet oxygen by the photosensitizers does not change; however, the generation efficiency of singlet oxygen decreases due to the shielding action of melanin.
A Chemist's View of Melanogenesis
Pigment Cell Research, 2003
The significance of our understanding of the chemistry of melanin and melanogenesis is reviewed. Melanogenesis begins with the production of dopaquinone, a highly reactive o-quinone. Pulse radiolysis is a powerful tool to study the fates of such highly reactive melanin precursors. Based on pulse radiolysis data reported by Land et al. (J Photochem Photobiol B: Biol 2001;64:123) and our biochemical studies, a pathway for mixed melanogenesis is proposed. Melanogenesis proceeds in three distinctive steps. The initial step is the production of cysteinyldopas by the rapid addition of cysteine to dopaquinone, which continues as long as cysteine is present (1 lM). The second step is the oxidation of cysteinyldopas to give pheomelanin, which continues as long as cysteinyldopas are present (10 lM). The last step is the production of eumelanin, which begins only after most cysteinyldopas are depleted. It thus appears that eumelanin is deposited on the preformed pheomelanin and that the ratio of eu-to pheomelanin is determined by the tyrosinase activity and cysteine concentration. In eumelanogenesis, dopachrome is a rather stable molecule and spontaneously decomposes to give mostly 5,6dihydroxyindole. Dopachrome tautomerase (Dct) catalyses the tautomerization of dopachrome to give mostly 5,6-dihydroxyindole-2-carboxylic acid (DHICA). Our study confirmed that the role of Dct is to increase the ratio of DHICA in eumelanin and to increase the production of eumelanin. In addition, the cytotoxicity of o-quinone melanin precursors was found to correlate with binding to proteins through the cysteine residues. Finally, it is still unknown how the availability of cysteine is controlled within the melanosome.
Chemical degradation of melanins: application to identification of dopamine-melanin
Pigment cell research / sponsored by the European Society for Pigment Cell Research and the International Pigment Cell Society, 1998
Melanocytes produce two chemically distinct types of melanin pigments, eumelanins and pheomelanins. These pigments can be quantitatively analyzed by acidic KMnO4 oxidation or reductive hydrolysis with hydriodic acid (HI) to form pyrrole-2,3,5-tricarboxylic acid (PTCA) or aminohydroxyphenylalanine (AHP), respectively. Dark brown melanin-like pigments are also widespread in nature, for example, in the substantia nigra of humans and primates (neuromelanin), in butterfly wings and in the fungus Cryptococcus neoformans. To characterize such diverse types of melanins, we have improved the alkaline H2O2 oxidation method of Napolitano et al. (Tetrahedron, 51:5913-5920, 1995) and re-examined the HI hydrolysis method of Wakamatsu et al. (Neurosci. Lett., 131:57-60, 1991). The results obtained with H2O2 oxidation show that 1) pyrrole-2,3-dicarboxylic acid (PDCA), a specific marker of 5,6-dihydroxyindole units in melanins, is produced in yields ten times higher than by acidic KMnO4 oxidation, a...
Photochemistry and Photobiology, 1984
Photoinduced oxygen consumption in systems containing synthetic and natural pheomelanins has been studied by ESR spectroscopy using a nitroxide spin probe to monitor oxygen concentration. Action spectra and quantum yields have been determined for melanin from 5-S-cysteinyldopa and for pheomelanins extracted from red human hair and red chicken feathers. For comparison, data also were obtained for eumelanins from black hair and black feathers. The action spectrum for oxygen consumption by cysteinyldopa melanin is closely related to that previously obtained for eumelanins except that it shows slightly less efficiency at intermediate wavelengths (ca. 300-400 nm). Action spectra for the natural pheomelanins resemble either that for cysteinyldopa melanin or that for eumelanin. In general pheomelanins are no more effective than eumelanins in promoting oxygen consumption, i.e. they are no more susceptible to net photooxidation.
Chemistry of Mixed Melanogenesis—Pivotal Roles of Dopaquinone
Photochemistry and Photobiology, 2008
Melanins can be classified into two major groups-insoluble brown to black pigments termed eumelanin and alkali-soluble yellow to reddish-brown pigments termed pheomelanin. Both types of pigment derive from the common precursor dopaquinone (ortho-quinone of 3,4-dihydroxyphenylalanine) which is formed via the oxidation of L-tyrosine by the melanogenic enzyme tyrosinase. Dopaquinone is a highly reactive ortho-quinone that plays pivotal roles in the chemical control of melanogenesis. In the absence of sulfhydryl compounds, dopaquinone undergoes intramolecular cyclization to form cyclodopa, which is then rapidly oxidized by a redox reaction with dopaquinone to give dopachrome (and dopa). Dopachrome then gradually and spontaneously rearranges to form 5,6-dihydroxyindole and to a lesser extent 5,6-dihydroxyindole-2-carboxylic acid, the ratio of which is determined by a distinct melanogenic enzyme termed dopachrome tautomerase (tyrosinase-related protein-2). Oxidation and subsequent polymerization of these dihydroxyindoles leads to the production of eumelanin. However, when cysteine is present, this process gives rise preferentially to the production of cysteinyldopa isomers. Cysteinyldopas are subsequently oxidized through redox reaction with dopaquinone to form cysteinyldopaquinones that eventually lead to the production of pheomelanin. Pulse radiolysis studies of early stages of melanogenesis (involving dopaquinone and cysteine) indicate that mixed melanogenesis proceeds in three distinct stages-the initial production of cysteinyldopas, followed by their oxidation to produce pheomelanin, followed finally by the production of eumelanin. Based on these data, a casing model of mixed melanogenesis is proposed in which a preformed pheomelanic core is covered by a eumelanic surface. †This invited paper is part of the Symposium-in-Print: Melanins.