title: Kinetic analysis and modelling of the allosteric behaviour of liver and muscle glycogen phosphorylases.
abstract: Allosteric enzymes have very complex kinetic behaviours which are primarily interpreted through simplified models. To describe the functional properties of liver and muscle glycogen phosphorylase isozymes we have developed an experimental strategy based on the measurements of initial reaction rates in the presence of different concentrations of the effectors glucose-1-phosphate and methyl-xanthines. Using the extensive structural information available for the two glycogen phosphorylase conformers T (inactive) and R (active) with different ligands, we have applied the Monod-Wyman-Changeux model and analysed the results in the context of the exclusive binding of the inhibitors to the T state, meanwhile the substrate glucose-1-phosphate binds to both, the R and T states. The kinetic analysis shows a good agreement between our model and the results obtained from the glycogen phosphorylases and inhibitors included in this study, which demonstrates the validity of the approach described here.
authors.affiliation: Department of Physical Chemistry, Biochemistry and Inorganic Chemistry, University of Almería, 04120 Almería, Spain.
authors.forename: Celia
authors.initials: C
authors.lastname: Cuadri-Tomé
authors.forename: Carmen
authors.initials: C
authors.lastname: Barón
authors.forename: Vicente
authors.initials: V
authors.lastname: Jara-Pérez
authors.forename: Antonio
authors.initials: A
authors.lastname: Parody-Morreale
authors.forename: Jose C
authors.initials: JC
authors.lastname: Martinez
authors.forename: Ana
authors.initials: A
authors.lastname: Cámara-Artigas
mesh_terms: D000494:Allosteric Regulation; D000495:Allosteric Site; D000818:Animals; D002110:Caffeine / Q000378:metabolism; D025001:Glycogen Phosphorylase, Liver Form / Q000737:chemistry* / Q000378:metabolism*; D024982:Glycogen Phosphorylase, Muscle Form / Q000737:chemistry* / Q000378:metabolism*; D007700:Kinetics; D008958:Models, Molecular; D011485:Protein Binding; D011817:Rabbits; D014970:Xanthines / Q000378:metabolism
chemical_list: D014970:Xanthines; D002110:Caffeine; C053085:1-methylxanthine; D025001:Glycogen Phosphorylase, Liver Form; D024982:Glycogen Phosphorylase, Muscle Form