β-Citryl-L-glutamate Is an Endogenous Iron Chelator That Occurs Naturally in the Developing Brain
β-Citryl-L-glutamate Is an Endogenous Iron Chelator That Occurs Naturally in the Developing Brain
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DOI：
10.1248/bpb.33.729
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发表时间：
2010-05-01
影响因子：
2
通讯作者：
Miyake, Masaharu
中科院分区：
文献类型：
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作者：
Hamada-Kanazawa, Michiko;Kouda, Makiko;Miyake, Masaharu
化合物β-柠檬基-L-谷氨酸(β-CG)最初是从发育中的大脑中分离出来的，同时在睾丸和眼睛中也发现了高浓度的它。然而，它的功能作用尚不清楚。为了评价其与金属离子的配位作用，我们进行了pH滴定实验。根据pH滴定数据计算了M-p(β-CG)(Q)H-r的稳定常数logβ(PQR)，结果表明，β-CG与Fe(III)、Cu(II)、Fe(II)和Zn(II)形成较强的络合物。β-CG对Fe(OH)(2)的增溶效果比从Fe(OH)(3)的增铁效果更好。因此，我们研究了β-CG对铁依赖的活性氧(ROS)生成系统的影响，以及β-CG和金属离子-(β-CG)络合物潜在的清除ROS的活性。β-CG以剂量依赖的方式抑制铁依赖的脱氧核糖降解和铁依赖的DNA或质粒DNA损伤，而对铜介导的DNA损伤无影响。此外，热力学数据表明，在生理pH溶液中，β-CG是Fe(II)的螯合剂，而不是Fe(III)的螯合剂。综上所述，这些发现表明β-CG是一种内源性低分子铁络合剂。
The compound beta-citryl-L-glutamate (beta-CG) was initially isolated from developing brains, while it has also been found in high concentrations in testes and eyes. However, its functional roles are unclear. To evaluate its coordination with metal ions, we performed pH titration experiments. The stability constant, log beta(pqr) for M-p(beta-CG)(q)H-r was calculated from pH titration data, which showed that beta-CG forms relatively strong complexes with Fe(III), Cu(II), Fe(II) and Zn(II). beta-CG was also found able to solubilize Fe more effectively from Fe(OH)(2) than from Fe(OH)(3). Therefore, we examined the effects of beta-CG on Fe-dependent reactive oxygen species (ROS)-generating systems, as well as the potential ROS-scavenging activities of beta-CG and metal ion-(beta-CG) complexes. beta-CG inhibited the Fe-dependent degradation of deoxyribose and Fe-dependent damage to DNA or plasmid DNA in a dose-dependent manner, whereas it had no effect on Cu-mediated DNA damage. In addition, thermodynamic data showed that beta-CG in a physiological pH solution is an Fe(II) chelator rather than an Fe(III) chelator. Taken together, these findings suggest that beta-CG is an endogenous low molecular weight Fe chelator.