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.