title: Zero-order ultrasensitivity in the regulation of glycogen phosphorylase.
abstract: The activity of glycogen phosphorylase (1,4-alpha-D-glucan:orthophosphate alpha-D-glucosyltransferase, EC 2.4.1.1) is controlled by a cyclic phosphorylation-dephosphorylation process through the action of the interconverting enzymes, phosphorylase b kinase (ATP:phosphorylase-b phosphotransferase, EC 2.7.1.38) and phosphorylase a phosphatase (phosphorylase a phosphohydrolase, EC 3.1.3.17). In muscle tissue, the combined concentration of the activated (phospho-) form, phosphorylase a, and the nonactivated (dephospho-) form, phosphorylase b, is substantially greater than the Km of either of the interconverting enzymes for its phosphorylase substrate. It has been predicted that, under such a set of conditions, a sensitivity amplification will occur for phosphorylase regulation due to the zero-order ultrasensitivity effect [LaPorte, D. C. & Koshland, D. E., Jr. (1983) Nature (London) 305, 286-290]. The sensitivity amplification will enhance the responsiveness of the phosphorylase interconversion cycle to changes in the ratio of activities of the kinase to phosphatase. We have studied the cyclic interconversion process using purified muscle enzymes in steady-state reactions and found that there is an enhancement in the control sensitivity of the process due to the zero-order ultrasensitivity effect. The potential for the in vivo enhancement of sensitivity in glycogen degradation by this effect is discussed.
authors.forename: M H
authors.initials: MH
authors.lastname: Meinke
authors.forename: J S
authors.initials: JS
authors.lastname: Bishop
authors.forename: R D
authors.initials: RD
authors.lastname: Edstrom
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D006003:Glycogen / Q000378:metabolism; D007700:Kinetics; D009132:Muscles / Q000201:enzymology; D010764:Phosphorylase Kinase / Q000378:metabolism; D010765:Phosphorylase Phosphatase / Q000378:metabolism; D006005:Phosphorylases / Q000378:metabolism*; D010766:Phosphorylation; D011817:Rabbits; D013552:Swine
chemical_list: D000255:Adenosine Triphosphate; D006003:Glycogen; D006005:Phosphorylases; D010764:Phosphorylase Kinase; D010765:Phosphorylase Phosphatase