Apr 1, 1976

Simple model for hormone-activated adenylate cyclase systems

Proceedings of the National Academy of Sciences of the United States of America
G G Hammes, M Rodbell

Abstract

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...Continue Reading

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References

Mentioned in this Paper

Guanosine
Glucagon (rDNA)
Glucagon
Glucagon Measurement
Adenylyl Cyclase 9
Nucleotides
Metabolic Inhibition
Adcy1
Hydrogen-Ion Concentration
Adenylate Cyclase

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