β-Citryl-L-glutamate (β-CG) is a unique compound initially isolated from developing brains, which also appears in high concentrations during the period characterized by growth and differentiation of neurons in developing animals, and then decreases with maturation. However, its functional roles remain unclear. The stability constant obtained in our previous pH titration studies showed that β-CG forms relatively strong complexes with copper. Reactive oxygen species (ROS) and nitric oxide (NO) have been suggested to act as mediators of the cell death that occurs in neurons during development of the nervous system. However, regulation of ROS and NO formation by Cu in the developing brain remains poorly understood. The activity of superoxide dismutase (SOD), a key superoxide scavenging enzyme, is low in the developing brain. Furthermore, xanthine oxidase (XO) has been implicated in diverse pathological situations due to its capability of generating both ROS and NO. Therefore, we examined the effects of β-CG and its Cu-complex on SOD and XO activities. We found that the [Cu(II)(β-CG)] complex had SOD activity and a strong competitive inhibition of XO, while reduced glutathione caused concentration-dependent decreases of the XO inhibitory activities in the [Cu(II)(β-CG)] complex.
2010 The Pharmaceutical Society of Japan