Inhibitory Effect of Zinc and Copper on Phophatase Activity in the Brain Cytosol of Rats : Involvement of SH Groups

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The effect of various metal ions on neutral phosphatase activity in the brain cytosol of rats was investigated. p-Nitrophenylphosphate was used as the substrate for the enzyme assay. Brain cytosolic phophatase activity was significantly decreased by the presence of zinc or copper in the range of 10^<-5> to 10^<-3> M in the enzyme reaction mixture, while it was significantly increased by manganse, nickel or cobalt (10^<-5> to 10^<-3> M). Calcium (10^<-5> to 10^<-3> M) did not have an appreciable effect on brain cytosolic phosphatase activity. The inhibitory effect of zinc (10^<-5> M) or copper (10^<-5> M) on phosphatse activity was seen in the presence o manganese, nickel or cobalt with 10^<-4> M concentration, indicating a potent inhibitory effect of these metals. Zinc or copper-decreased phosphatase activity was clearly prevented by dithiothreitol (5 mM), although the effect of each metal was further enhanced by N-ethylmaleimide (5 mM), suggesting that the metals act on the SH-groups of enzyme. Moreover, the inhibitory effect of zinc (10^<-5> M) was significantly enhanced by S-100A (10^<-6> M) or calbindin (10^<-7> M), although neither protein had any effect in the presence of calcium (10^<-5> M) or copper (10^<-5> M). These results suggests that zinc has an unique role in the regulation of neutral phosphatase activity in rat brain cytosol.
公益社団法人日本薬学会の論文
1998-11-15