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

Gregory Quarforth, Khalil Ahmed, Donald Foster, Leslie Zieve

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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 Km 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.

Original languageEnglish (US)
Pages (from-to)1039-1044
Number of pages6
JournalBiochemical Pharmacology
Issue number9
StatePublished - May 1 1976


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