Phosphorylase a is an allosteric inhibitor of the glycogen and microsomal forms of rat hepatic protein phosphatase-1.
The dephosphorylation of glycogen synthase by protein phosphatase-1 in hepatic glycogen and microsomes was inhibited by nanomolar concentrations of phosphorylase a. The I50 for phosphorylase a was 1000-fold lower than its Km as a substrate, while tryptic digestion increased the I50 1000-fold without affecting Km. Protein phosphatase-1 from skeletal muscle and protein phosphatase-2A from liver were only inhibited at 1000-fold higher concentrations. Protein phosphatase-1 became desensitized to phosphorylase a when released from hepatic microsomes, but sensitivity was partially restored by readdition of the solubilized enzyme to the microsomes. The results demonstrate that phosphorylase a is a potent allosteric inhibitor of hepatic protein phosphatase-1 and suggest that inhibition may be conferred by a novel phosphorylase a-binding subunit.
D000494:Allosteric Regulation; D000818:Animals; D006006:Glycogen Synthase / Q000378:metabolism; D006007:Glycogen-Synthase-D Phosphatase / Q000037:antagonists & inhibitors*; D066298:In Vitro Techniques; D008112:Liver Glycogen / Q000378:metabolism; D008862:Microsomes, Liver / Q000201:enzymology*; D009132:Muscles / Q000378:metabolism; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors*; D010764:Phosphorylase Kinase / Q000378:metabolism; D010762:Phosphorylase a / Q000494:pharmacology*; D006005:Phosphorylases / Q000494:pharmacology*; D010766:Phosphorylation; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2; D051381:Rats
D008112:Liver Glycogen; D010762:Phosphorylase a; D006005:Phosphorylases; D006006:Glycogen Synthase; D010764:Phosphorylase Kinase; D010749:Phosphoprotein Phosphatases; D054645:Protein Phosphatase 1; D054648:Protein Phosphatase 2; D006007:Glycogen-Synthase-D Phosphatase