Action of methanethiol on membrane (Na⁺, K⁺)-ATPase of rat brain

The action of methanethiol (CH₃SH) on rat brain (Na⁺, K⁺)-ATPase was examined. The results show that CH₃SH acts at several sites on the enzyme system. The effects are characterized by an inhibition of the ATPase activity, but a concurrent stimulation of the associated K⁺-dependent phosphatase. The inhibitory effect of CH₃SH was of an apparently mixed type with respect to the activation of the ATPase by Na⁺ or by ATP suggesting that CH₃SH may inhibit the formation of phosphoenzyme intermediate in the ATPase reaction, and the inhibition may not be fully reversed by increasing Na⁺. Methanethiol inhibited the activation of the ATPase by K⁺ in an apparently uncompetitive manner, whereas it produced a competitive stimulation of the K⁺ activation of the K⁺-dependent phosphatase activity by increasing the affinity of K⁺ for the enzyme. There was no significant change in the apparent K_m for the substrate p-nitrophenyl phosphate for the phosphatase activity. These effects of CH₃SH may be relevant to its toxicity, and offer a possible molecular site of its action with implications for the encephalopathy of hepatic failure.