Activation of hepatocyte glycogen synthase by metabolic inhibitors.
Incubation of isolated rat hepatocytes with metabolic inhibitors causes an increase in the -glucose 6-P/+glucose 6-P activity ratio of glycogen synthase after decreasing ATP and increasing AMP levels. Concomitantly, the activity of phosphorylase is increased six-fold by the same treatment. This activation of both enzymes remains after gel filtration of the hepatocyte extracts. Addition of metabolic inhibitors to cells pretreated with an inhibitor of AMP-deaminase results in an accumulation of AMP and, simultaneously, in a further increase in the activation state of glycogen synthase. The correlation coefficient between the intracellular concentration of AMP and glycogen synthase activity is r = 0.93. It is proposed that the covalent activation of glycogen synthase by metabolic inhibitors can be triggered by changes in the level of the intracellular concentrations of adenine nucleotides.
D019297:2,4-Dinitrophenol; D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000227:Adenine Nucleotides / Q000378:metabolism; D000818:Animals; D001278:Atractyloside / Q000031:analogs & derivatives / Q000494:pharmacology; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D004140:Dinitrophenols / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D006006:Glycogen Synthase / Q000378:metabolism*; D007291:Inosine Monophosphate / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D006005:Phosphorylases / Q000378:metabolism; D051381:Rats
D000227:Adenine Nucleotides; D004140:Dinitrophenols; D007291:Inosine Monophosphate; D001278:Atractyloside; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; C010192:9-(2-hydroxy-3-nonyl)adenine; D006005:Phosphorylases; D006006:Glycogen Synthase; D000225:Adenine; D019297:2,4-Dinitrophenol; C003853:carboxyatractyloside