β-Citryl-L-glutamate Is an Endogenous Iron Chelator That Occurs Naturally in the Developing Brain

抄録

The compound β-citryl-L-glutamate (β-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, logβ_pqr for M_p(β-CG)_qH_r was calculated from pH titration data, which showed that β-CG forms relatively strong complexes with Fe(III), Cu(II), Fe(II) and Zn(II). β-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 β-CG on Fe-dependent reactive oxygen species (ROS)-generating systems, as well as the potential ROS-scavenging activities of β-CG and metal ion-(β-CG) complexes. β-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 β-CG in a physiological pH solution is an Fe(II) chelator rather than an Fe(III) chelator. Taken together, these findings suggest that β-CG is an endogenous low molecular weight Fe chelator.