3':5'-cyclic adenosine monophosphate phosphodiesterase: negative cooperativity.
Kinetic and chromatographic analysis of cyclic nucleotide phosphodiesterase (EC 3.1.4.c) obtained from rat tissue has revealed that this enzyme exists in at least two molecular forms. After chromatographic separation, one form (cyclic AMP phosphodiesterase) still exhibits kinetics suggestive of the action of either two enzymes or one enzyme under negative cooperative regulation. Computer model studies were undertaken to distinguish between these two possibilities. The matrix method was used to generate the partition functions for (a) the sum of two independent enzymes and (b) one enzyme exhibiting negative cooperative kinetics. The experimental data were fitted to the theoretical models by a nonlinear least-squares computer program. The results show that, while both models can fit the data, the two-enzyme model would require contamination far in excess of what is detectable physically or by activity measurements. Thus, the negative cooperative model seems the more appropriate theoretical explanation of the observed kinetic behavior of this enzyme. The implication of negative cooperativity with respect to the regulation of cyclic AMP concentrations in physiological systems is discussed.
D000273:Adipose Tissue / Q000201:enzymology; D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000201:enzymology; D002462:Cell Membrane / Q000201:enzymology; D002848:Chromatography, DEAE-Cellulose; D002850:Chromatography, Gel; D003201:Computers; D000242:Cyclic AMP; D004912:Erythrocytes / Q000166:cytology / Q000201:enzymology; D007668:Kidney / Q000201:enzymology; D007700:Kinetics; D008433:Mathematics; D008956:Models, Chemical; D009132:Muscles / Q000201:enzymology; D009206:Myocardium / Q000201:enzymology; D010727:Phosphoric Diester Hydrolases / Q000302:isolation & purification; D010744:Phosphoric Monoester Hydrolases; D011487:Protein Conformation; D051381:Rats; D014316:Tritium
D014316:Tritium; D000242:Cyclic AMP; D010744:Phosphoric Monoester Hydrolases; D010727:Phosphoric Diester Hydrolases