A chemist's view of melanogenesis
A chemist's view of melanogenesis
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DOI：
10.1034/j.1600-0749.2003.00037.x
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发表时间：
2003-06-01
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影响因子：
--
通讯作者：
Ito, S
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文献类型：
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作者：
Ito, S
我们的理解的意义黑色素和黑色素生成的化学进行了审查。黑素生成开始于多巴醌的产生，多巴醌是一种高活性的邻醌。脉冲辐解是研究这种高活性黑色素前体命运的有力工具。基于Land等人报告的脉冲辐解数据。（J Photochem Photobiol B：Biol 2001;64：123）和我们的生物化学研究，提出了混合黑素生成的途径。黑素生成分为三个不同的步骤。初始步骤是通过将半胱氨酸快速加入到多巴醌中来产生半胱氨酰多巴，只要半胱氨酸存在（1 μ M），该步骤就继续进行。第二步是半胱氨酰多巴氧化生成褐黑素，只要存在半胱氨酰多巴（10 μ M），该反应就继续进行。最后一步是产生真黑素，这只有在大多数半胱氨酰多巴耗尽后才开始。因此，似乎真黑素沉积在预先形成的褐黑素上，并且真黑素与褐黑素的比率由酪氨酸酶活性和半胱氨酸浓度决定。在真黑素发生中，多巴色素是一种相当稳定的分子，并自发分解，主要产生5，6-二羟基吲哚。多巴色素互变异构酶（Dct）催化多巴色素的互变异构化，主要产生5，6-二羟基吲哚-2-羧酸（DHICA）。我们的研究证实，Dct的作用是增加DHICA在真黑素中的比例，增加真黑素的产量。此外，发现邻醌黑色素前体的细胞毒性与通过半胱氨酸残基与蛋白质的结合相关。最后，仍然不知道半胱氨酸的可用性是如何在黑素体内控制的。
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 muM). The second step is the oxidation of cysteinyldopas to give pheomelanin, which continues as long as cysteinyldopas are present (10 muM). 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 5,6-dihydroxyindole. 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.