Simple model for hormone-activated adenylate cyclase systems.
A simple model is developed to explain the activation of rat liver plasma membrane adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] by guanosine nucleotides and glucagon and the dependence of the cATALYTIC RATE ON Mg2+, H+, and substrate concentrations. The basic model proposes that the adenylate cyclase system can exist in two states, A and B; that activating ligands bind preferentially to the B state; and that only the B state is active. Kinetic data are quantitatively fit to this model, and the binding constants for the interaction of the A and B states with glucagon, GTP, and guanyl-5'-ylimidodiphosphate are obtinaed. The substrates ATP and adenyl-5'-ylimidodiphosphate appear to show little preference between the A and B states, and simple Michaelis-Menten kinetics are sufficient to describe the dependence of the catalytic rate on substrate concentration under optimal conditions. The dependence of the rate on pH can be explained by postulating that one ionizable group in its acid form and one ionizable group in its basic form must be present at the active site in order for catalysis to occur. The activation and inhibition of the activity by Mg2+ can be explained by a similar mechanism with Mg2+ binding to activating and inhibiting sites. Glucagon and guanosine nucleotides appear to influence the dependence of the rate on Mg2+ and glucagon. The Mg2+ also may display some preference for the B state. A comparison of this model with others that have been proposed is given. The proposed model appears to provide a simple conceptual frame-work that is applicable to many adenylate cyclase systems.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D004789:Enzyme Activation / Q000187:drug effects; D005934:Glucagon / Q000494:pharmacology*; D006150:Guanine Nucleotides; D006863:Hydrogen-Ion Concentration; D008099:Liver / Q000201:enzymology; D008274:Magnesium / Q000494:pharmacology; D008954:Models, Biological; D051381:Rats
D006150:Guanine Nucleotides; D005934:Glucagon; D000262:Adenylyl Cyclases; D008274:Magnesium