CONTROL OF HEPATIC PHOSPHORYLASE-PHOSPHATASE BY ATP, ADP AND MG2+

1. 1. The effects of ATP, ADP, Mg2+ and pH on three different preparations of hepatic phosphorylase phosphatase (phosphorylase α phosphohydrolase, EC 3.1.3.17) were investigated. 2. 2. The phosphorylase phosphatase activity in these preparations was decreased by ATP, ADP, adenylyl imidodiphosphate and by Mg2+. The effect produced by the adenine nucleotides was less pronounced at high pH than at low pH. 3. 3. Increasing concentrations of Mg2+, Mn2+ and Ca2+ in the presence of a constant concentration of ATP prevented the effect of ATP. At high concentrations the divalent cations decreased the reaction rate of the phosphatase in the presence of ATP as in its absence. At pH 7.5 and 8.5, ATP and Mg2+ in equimolar concentrations decreased the phosphatase activity to a smaller extent than ATP alone. 4. 4. The activity of phosphorylase phosphatase was progressively less affected if ATPMg2- and free Mg2+ were increased at constant concentrations of uncomplexed ATP. In the concentration range expected to occur in the intact cell an increasing degree of complexation of ATP with Mg2+ diminished the inhibitory effect of the nucleotide. Since addition of Mg2+ after the preincubation with free ATP did not reverse the loss of phosphatase activity we concluded that the mechanism of action of ATP and ADP is not a simple inhibition as defined by an immediate and reversible loss of activity after the binding of a ligand. © 1979.