Studies on allosteric phenomena in glycogen phosphorylase b.
This article attempts to trace, from a personal point of view, the history of discoveries of allosteric phenomena in phosphorylase b and the later development of systematic attempts to fit the data into comprehensive theoretical models. Work from our own laboratory is emphasized, but we try to integrate this into the results from other investigators and show their contributions to our ideas and experiments. Finally, some recent unpublished data is presented together with some conclusions and predictions from a new hypothesis. The discoveries by Carl and Gerty Cori of the activation of phosphorylase by AMP, the inhibition of glucose and the enzymatic interconversion of two forms fo the enzyme with different control properties helped lay the foundations of our present understanding of allosteric mechanisms. The later discovery of the oligomeric nature of phosphorylase and its relationship to AMP binding served as a basis for many years of research into the structure-function relationships of phosphorylase and other enzymes. Data showing that AMP lowers the entropy of activation is discussed with respect to the role of the nucleotide and its binding close to the active site. The discovery of the control of phosphorylase b by common metabolites and the impetus this gave to the intensive kinetic studies of the last ten years, wherein fitting to theoretical models has been a common feature, is reviewed.
D000249:Adenosine Monophosphate / Q000494:pharmacology; D000494:Allosteric Regulation; D000495:Allosteric Site; D000818:Animals; D002151:Calorimetry; D004789:Enzyme Activation / Q000187:drug effects; D005958:Glucosephosphates / Q000494:pharmacology; D007700:Kinetics; D010710:Phosphates / Q000494:pharmacology; D006005:Phosphorylases / Q000378:metabolism; D011485:Protein Binding; D013816:Thermodynamics
D005958:Glucosephosphates; D010710:Phosphates; D000249:Adenosine Monophosphate; D006005:Phosphorylases