The control of liver glycogen synthetase phosphatase by phosphorylase.

Abstract

The activation of glycogen synthetase in a liver gel filtrate and the latency by which it is normally preceded have been studied in conditions where the level of phosphorylase a was greatly modified by the addition of either the pure enzyme or of antibodies directed against it. In the presence of liver or muscle phorphorylase a, glycogen synthetase phosphatase was nearly inactive; phosphorylase b had only a slight effect. Antibodies, obtained in the rabbit against dog liver phosphorylase, strongly depressed the activity of phosphorylase a in a mouse liver preparation; they simultaneously allowed an immediated activation of glycogen synthetase.These results indicate that the lag period that precedes that activation of glycogen synthetase in a liver filtrate is the time required for the conversion of phosphorylase a into b by phosphorylase phosphatase. The previously reported shortening of the lag period by glucose, caffeine and nicotinamide or by a tratment with glucocorticoids is entirely explained by the faster inactivation of phosphorylase in the same conditions. The elongation of the lag period by glycogen and its supporession by AMP and magnesium remained however to be explained. It has been shown that the dose of glycogen that prolongs the lag period also inhibits phosphorylase posphatase, wherease AMP and magnesium counteract the inhibition of synthetase phosphatase by phosphorylase a.