The effect of glucose on liver glycogen synthase phosphatase activity in the presence of ATP-Mg

Abstract

Glycogen particle synthase phosphatase activity is stimulated by glucose with an A 0.5 of approximately 27 m m. The A 0.5 is higher than the usual concentrations present in the liver. However, in vitro, certain methylxanthines such as caffeine or theophylline reduce the glucose A 0.5 to approximately 10 m m, a concentration well within the normal range of liver glucose concentrations. Methylxanthines do not affect the maximum stimulation by glucose (2.3-fold greater than control rate). The phosphatase reaction also is inhibited by ATP-Mg ( I 0.5 = 0.1 mM). In the present studies, we have determined the interaction of these effectors. The presence of ATP-Mg at a concentration of 3 m m only slightly reduced the maximal stimulation by glucose. The A 0.5 for glucose was unaffected (24 m m). The synergistic effect of caffeine with glucose also was not changed by the presence of ATP-Mg. The A 0.5 for glucose was reduced to 11 m m, similar to that in the absence of ATP-Mg. In addition, maximum stimulation by glucose was unchanged. Similar results were obtained when theophylline replaced caffeine. We conclude that the ATP-Mg binding site on either the phosphatase or its substrate, synthase D, does not influence the glucose and methylxanthine binding sites. Effectively, ATP-Mg increased the range over which glucose stimulates the phosphatase activity. In the presence of ATP-Mg, the maximum stimulation by glucose is approximately 7-fold; whereas, in the absence of ATP-Mg it is approximately 2.3-fold. Thus, ATP-Mg may serve to increase the sensitivity of the synthase phosphatase reaction to glucose regulation under in vivo conditions.