TY - JOUR
T1 - Action of methanethiol on membrane (Na+, K+)-ATPase of rat brain
AU - Quarforth, Gregory
AU - Ahmed, Khalil
AU - Foster, Donald
AU - Zieve, Leslie
PY - 1976/5/1
Y1 - 1976/5/1
N2 - 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.
AB - 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.
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U2 - 10.1016/0006-2952(76)90493-7
DO - 10.1016/0006-2952(76)90493-7
M3 - Article
C2 - 131559
AN - SCOPUS:0017286838
SN - 0006-2952
VL - 25
SP - 1039
EP - 1044
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
IS - 9
ER -