Equilibrium kinetics model for the cGMP-stimulated phosphodiesterase of brain coated vesicles.
An equilibrium kinetics model is proposed to described some of the enzymatic properties of the cyclic GMP-stimulated phosphodiesterase activity associated with brain clathrin coated vesicles. The model assumes the presence of pharmacologically distinct regulatory and catalytic domains in the enzyme. The model contemplates that random fashion occupancy of the regulatory site by the substrate, cyclic GMP, induces a conformational change which leads to the generation of an actived catalytic state. Therefore, cyclic GMP is a positive allosteric modulator of the coated vesicle enzyme. Experimental data revealed that occupancy or activation of the regulatory site was not essential for catalysis to occur since hydrolysis occurred after loss (200%) of the activation by cyclic GMP. This constitutes an example of non-essential substrate activation. Analysis of this PDE following activation by cGMP and after loss of the regulation, activation capacity of the enzyme allows the calculation of the various kinetic parameters inherent in the model.
Silva
W I
WI
Department of Pharmacology, University Central del Caribe, School of Medicine, Cayey, P.R. 00634.
Puszkin
S
S
D015106:3',5'-Cyclic-GMP Phosphodiesterases / Q000378:metabolism*; D000494:Allosteric Regulation; D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000648:ultrastructure; D002417:Cattle; D003034:Coated Pits, Cell-Membrane / Q000201:enzymology*; D006152:Cyclic GMP / Q000378:metabolism; D004789:Enzyme Activation; D007700:Kinetics; D008954:Models, Biological
D015106:3',5'-Cyclic-GMP Phosphodiesterases; D006152:Cyclic GMP