Publications [#112962] of G Vann V. Bennett

Papers Published

1. S Jacobs, V Bennett, P Cuatrecasas, Kinetics of irreversible activation of adenylate cyclase of fat cell membranes by phosphonium and phosphoramidate analogs of gtp1., Journal of cyclic nucleotide research, UNITED STATES, vol. 2 no. 4 , pp. 205-23, ISSN 0095-1544
   (last updated on 2003/02/18)

   Abstract:
   The ability of guanylylimidodiphosphate (GMP=P(NH)P) and guanylylmethylenediphosphonate (GMP-P(CH2)P) to activate adenylate cyclase activity has been studied by incubating these analogs with fat cell membranes followed by thorough washing of the membranes before assay of enzyme activity. GMP-P(NH)P is hydrolyzed by membrane preparations from several tissues. A pyruvate kinase regenerating system maintains the concentration of GMP-P(NH)P and thereby augments the ability of suboptimal concentrations of GMP-P(NH)P to activate adenylate cyclase. GTP inhibits activation of fat cell membrane adenylate cyclase by GMP-P(NH)P but this inhibition is overcome by time. This is consistent with the virtually irreversible nature of the GMP-P(NH)P activation, and with the inability of GTP to reverse the stimulated state of the enzyme. Although the initial rate of enzyme activation is highly dependent on the concentration of GMP-P(NH)P, with increasing times of incubation nearly the same maximal extent of activation is seen over a wide range of concentrations. Thus, it is not possible to estimate true affinity constants (at equilibrium) for GMP-P(NH)P, as anticipated from the virtually irreversible character of the activation process.

   Keywords:
   Adenylate Cyclase • Adipose Tissue • Adrenocorticotropic Hormone • Amides • Animals • Cell Membrane • Enzyme Activation • Erythrocytes • Guanosine Triphosphate • Isoproterenol • Kinetics • Magnesium • Phosphonic Acids • Rats • Turkeys • analogs & derivatives* • drug effects • enzymology • enzymology* • metabolism* • pharmacology • pharmacology*