Hadi N, Malik A, Azam S, Khan N U, Iqbal J
Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh (U.P.) 202 002, India.
Toxicol In Vitro. 2002 Dec;16(6):669-74. doi: 10.1016/s0887-2333(02)00083-8.
It has been proposed that considerable DNA damage may be caused by endogenous metabolites produced during the body's normal metabolic processes. 5-hydroxytryptamine (serotonin) is an important neurotransmitter in brain and spinal cord. We have previously shown that serotonin induces oxidative cleavage of DNA strands in the presence of copper ions. In the present paper we have examined the mechanism of copper binding by serotonin using absorption spectroscopy, Cu(II)-mediated lipid peroxidation and by determining the oxidation of the serotonin molecule. Addition of increasing concentrations of Cu(II) to serotonin leads to a progressive enhancement in the absorption band and is accompanied by a shift towards a lower wavelength indicative of the formation of an oxidised species of serotonin. Studies with the structurally related molecules tryptophan and melatonin showed that only serotonin is able to reduce Cu(II) to Cu(I). Similarly, only serotonin was found to be able to abolish the copper-mediated peroxidation of mitochondria. These results suggested the involvement of the phenolic group in copper binding. Further, it was also shown that the binding of copper to serotonin leads to the formation of a quinone in the absence of molecular oxygen. Based on these results, a model has been proposed in which serotonin reduces two molar equivalents of Cu(II) to Cu(I) through a reaction involving two electron oxidation of the phenolic ring to a quinone methide.
有人提出，人体正常代谢过程中产生的内源性代谢产物可能会造成相当程度的DNA损伤。5-羟色胺（血清素）是脑和脊髓中的一种重要神经递质。我们之前已经表明，血清素在铜离子存在的情况下会诱导DNA链的氧化断裂。在本文中，我们使用吸收光谱法、铜（II）介导的脂质过氧化作用以及通过测定血清素分子的氧化作用，研究了血清素与铜结合的机制。向血清素中添加浓度不断增加的铜（II）会导致吸收带逐渐增强，并伴随着向较低波长的移动，这表明形成了血清素的氧化物种。对结构相关分子色氨酸和褪黑素的研究表明，只有血清素能够将铜（II）还原为铜（I）。同样，仅发现血清素能够消除铜介导的线粒体过氧化作用。这些结果表明酚基团参与了铜的结合。此外，还表明在没有分子氧的情况下，铜与血清素的结合会导致醌的形成。基于这些结果，提出了一个模型，其中血清素通过涉及酚环双电子氧化为醌甲基化物的反应将两摩尔当量的铜（II）还原为铜（I）。
