Potential role of serotonin as a biological reductant associated with copper transportation
Potential role of serotonin as a biological reductant associated with copper transportation
复制标题
血清素作为与铜运输相关的生物还原剂的潜在作用
DOI：
10.1016/j.jinorgbio.2019.110770
复制
发表时间：
2019
影响因子：
3.9
通讯作者：
Takashi Miura
中科院分区：
文献类型：
--
作者：
Kaede Saito;Kasumi Watanabe;Risa Yanaoka;Lisa Kageyama;Takashi Miura
5-羟色胺（5-HT）是一种神经递质，来源于色氨酸。由于羟基连接到吲哚核，5-HT表现出比色氨酸高得多的氧化还原活性。为了深入了解5-HT的氧化还原活性的生物相关性，研究了Cu（I）结合配体对5-HT介导的铜还原的影响。Cu（II）与甘氨酸[Cu（II）-Gly 2]络合的d-d跃迁带不受单独加入5-HT的影响，但当含硫醚的化合物与5-HT共存时减弱。随着Cu（II）-Gly 2的d-d跃迁带的消失，5-HT的5-羟基吲哚的π-π* 跃迁带出现红移，这与5-HT氧化后形成二聚体的现象一致。5-HT和铜之间的氧化还原反应也被一种肽加速，该肽由膜蛋白铜转运蛋白1（Ctr 1）胞外结构域中富含甲硫氨酸（Met）的区域组成。由于Ctr 1转运铜穿过质膜，对Cu（I）具有特异性，因此Ctr 1吸收铜需要将细胞外Cu（II）还原为Cu（I）。可以为Ctr 1提供Cu（I）的金属还原酶已在酵母中被鉴定，但尚未在哺乳动物中发现。这项研究的结果表明，Met丰富的区域在N-末端胞外结构域的Ctr 1促进5-HT介导的Cu（II）的还原，以获得Cu（I）通过非酶促过程。
Serotonin (5-HT) is a neurotransmitter that is derived from tryptophan. Owing to a hydroxyl group attached to the indole nucleus, 5-HT exhibits a considerably higher redox activity than tryptophan. To gain insight into the biological relevance of the redox activity of 5-HT, the effect of Cu(I)-binding ligands on the 5-HT-mediated copper reduction was investigated. The d-d transition band of Cu(II) complexed with glycine [Cu(II)-Gly2] was not affected by addition of 5-HT alone but was diminished when a thioether-containing compound coexists with 5-HT. Concomitant with disappearance of the d-d transition band of Cu(II)-Gly2, the π-π* transition band of 5-hydroxyindole of 5-HT exhibits a red-shift which is consistently explained by oxidation of 5-HT and subsequent formation of a dimeric species. The redox reactions between 5-HT and copper are also accelerated by a peptide composed of a methionine (Met)-rich region in the extracellular domain of an integral membrane protein, copper transporter 1 (Ctr1). Since Ctr1 transports copper across the plasma membrane with specificity for Cu(I), reduction of extracellular Cu(II) to Cu(I) is required for copper uptake by Ctr1. Metalloreductases that can donate Cu(I) for Ctr1 have been identified in yeast but not yet been found in mammals. The results of this study indicate that the Met-rich region in the N-terminal extracellular domain of Ctr1 promotes the 5-HT-mediated Cu(II) reduction in order to acquire Cu(I) via a non-enzymatic process.