beta-Citryl-L-glutamate is an endogenous iron chelator that occurs naturally in the developing brain.
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, logbeta(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.
Hamada-Kanazawa
Michiko
M
Department of Physiological Chemistry, Faculty of Pharmaceutical Sciences, Kobe-Gakuin University, Japan.
Kouda
Makiko
M
Odani
Akira
A
Matsuyama
Kaori
K
Kanazawa
Kiyoka
K
Hasegawa
Tatsuya
T
Narahara
Masanori
M
Miyake
Masaharu
M
D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001921:Brain / Q000254:growth & development / Q000378:metabolism*; D002417:Cattle; D004249:DNA Damage; D003855:Deoxyribose / Q000378:metabolism*; D005290:Ferric Compounds; D005296:Ferrous Compounds; D005971:Glutamates / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000378:metabolism*; D008670:Metals / Q000378:metabolism; D008970:Molecular Weight; D010957:Plasmids; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012995:Solubility
D000975:Antioxidants; D005290:Ferric Compounds; D005296:Ferrous Compounds; D005971:Glutamates; D007502:Iron Chelating Agents; D008670:Metals; D017382:Reactive Oxygen Species; D003855:Deoxyribose; C018491:beta-citrylglutamic acid; D007501:Iron