The effect of glucose and of a treatment by glucocorticoids on the activation in vitro of liver glycogen synthetase.

Abstract

The removal of glucose, AMP and other small molecules from mouse liver extract by filtration through Sephadex G-25 has allowed us to demonstrate that the activation in vitro of glycogen synthetase is much more rapidly attained in the presence of glucose and also when the animals have received prednisolone 3 h before sacrifice. These effects are the result of a shortening of the lag period that precedes the activation of the synthetase; they are conveniently studied in filtrates that have been enriched with sulfate or phosphate ions. Like glucose, caffeine and nicotinamide shorten the lag period and are without action when this period is over; α-particulate glycogen has the opposite effect. No lag period is observed in the presence of AMP, particularly when associated with magnesium acetate. When a liver Sephadex filtrate is incubated in the absence of salts, glycogen synthetase b is converted into a partially active form that is rapidly transformed into synthetase a upon the addition of salt. These results support the hypothesis that glycogen synthetase phosphatase is initially present in the liver filtrate as a b enzyme, active only in the presence of AMP and magnesium; this b form is converted into its active, a, homologue through the action of a synthetase phosphatase activating enzyme, which is more active after a treatment with glucocorticoids, is stimulated by glucose, caffeine and nicotinamide and inhibited by glycogen, AMP and fluoride.