The role of zinc and zinc-binding proteins in regulation of glutamic acid decarboxylase in brain.

At physiological concentrations, zinc stimulates the activity of pyridoxal kinase, enhancing the formation of pyridoxal phosphate, which in turn enhances the activity of glutamic acid decarboxylase. In toxic doses, zinc inhibits glutamic acid decarboxylase directly and may adversely influence the GABA receptor sites. Zinc-binding proteins, which are inducible by zinc, have been identified in brain and regulate the steady state concentration of free Zn2+. Since free Zn2+ is a potent inhibitor of numerous sulfhydryl-containing enzymes, including glutamic acid decarboxylase, we conclude that zinc-binding proteins not only may function as a physiological donors of Zn2+ to zinc apometalloenzymes, but also may play a decisive role in preventing CNS toxicity by preventing the rise of free Zn2+ in the brain.