Inhibition by glucose 6-phosphate of cyclic AMP-dependent protein kinase phosphorylation of glycogen synthase.
Cyclic AMP-dependent protein kinase phosphorylates and inactivates glycogen synthase. In the absence of cyclic AMP, glycogen synthase is able to partially activate cyclic AMP-dependent protein kinase, probably by inducing the dissociation of the catalytic and regulatory subunits. The activation of cyclic AMP-dependent protein kinase by glycogen synthase is greatly reduced by the addition of low, physiological concentrations of the allosteric activator of glycogen synthase, glucose 6-phosphate. This effect appears to be specific for both glycogen synthase as substrate of the kinase and for cyclic AMP-dependent protein kinase as glycogen synthase phosphorylating enzyme. The result is an apparent, although not real effect of glucose 6-phosphate as an inhibitor competing with cyclic AMP. The reported inhibition by insulin of the activity of cyclic AMP-dependent protein kinase in skeletal muscle may be explained by the increased intracellular levels of glucose 6-phosphate resulting from the action of the hormone on glucose transport.
Villar-Palasi
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Department of Pharmacology, Medical School University of Virginia, Charlottesville 22908.
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000494:pharmacology*; D006006:Glycogen Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009132:Muscles / Q000201:enzymology; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000302:isolation & purification; D011817:Rabbits
D005958:Glucosephosphates; D047428:Protein Kinase Inhibitors; D019298:Glucose-6-Phosphate; D000242:Cyclic AMP; D006006:Glycogen Synthase; D011494:Protein Kinases