Chemical analysis of late stages of pheomelanogenesis: conversion of dihydrobenzothiazine to a benzothiazole structure
Chemical analysis of late stages of pheomelanogenesis: conversion of dihydrobenzothiazine to a benzothiazole structure
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DOI：
10.1111/j.1755-148x.2009.00580.x
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发表时间：
2009-08-01
影响因子：
4.3
通讯作者：
Ito, Shosuke
中科院分区：
文献类型：
--
作者：
Wakamatsu, Kazumasa;Ohtara, Kazumi;Ito, Shosuke
P>黑素生成是一个复杂的途径，其起始于酪氨酸酶在半胱氨酸存在下氧化酪氨酸（或DOPA，3，4-二羟基苯丙氨酸），这导致5-S-半胱氨酰多巴及其异构体的产生。除此步骤外，除了可能产生的中间体二氢-1，4-苯并噻嗪-3-羧酸（DHBTCA）外，几乎没有得到澄清。因此，我们进行了详细的研究过程中，使用多巴和半胱氨酸和酪氨酸酶的生理酶的pheomelanogenesis。为了阐明后期的pheomelanogenesis，化学降解方法的还原水解与氢碘酸和碱性过氧化物氧化。结果表明：（1）DHBTCA在半胱氨酰多巴异构体消失后积累，（2）DHBTCA然后通过与多巴醌的氧化还原交换氧化形成邻醌亚胺，这导致产生具有苯并噻嗪部分的褐黑素，和（3）苯并噻嗪部分逐渐降解形成苯并噻唑部分。后一种过程与人红色毛发中苯并噻唑衍生单位的比例比小鼠黄色毛发中高得多的比例一致。这些发现可能与褐黑素的（光）毒性作用有关。
P>Pheomelanogenesis is a complex pathway that starts with the oxidation of tyrosine (or DOPA, 3,4-dihydroxyphenylalanine) by tyrosinase in the presence of cysteine, which results in the production of 5-S-cysteinyldopa and its isomers. Beyond that step, relatively little has been clarified except for a possible intermediate produced, dihydro-1,4-benzothiazine-3-carboxylic acid (DHBTCA). We therefore carried out a detailed study on the course of pheomelanogenesis using DOPA and cysteine and the physiological enzyme tyrosinase. To elucidate the later stages of pheomelanogenesis, chemical degradative methods of reductive hydrolysis with hydroiodic acid and alkaline peroxide oxidation were applied. The results show that: (1) DHBTCA accumulates after the disappearance of the cysteinyldopa isomers, (2) DHBTCA is then oxidized by a redox exchange with dopaquinone to form ortho-quinonimine, which leads to the production of pheomelanin with a benzothiazine moiety, and (3) the benzothiazine moiety gradually degrades to form a benzothiazole moiety. This latter process is consistent with the much higher ratio of benzothiazole-derived units in human red hair than in mouse yellow hair. These findings may be relevant to the (photo)toxic effects of pheomelanin.