Studies on the mechanism of adenosine 5'-monophosphate inhibition of bovine liver fructose 1,6-bisphosphatase.
Inhibition by adenosine 5'-monophosphate (AMP) of the forward reaction of fructose 1,6-bisphosphatase (FBPase) has been studied by means of progress curve analysis. The full time course of the FBPase reaction was followed by coupling the reaction to the enzymes phosphoglucoisomerase and glucose-6-phosphate dehydrogenase. The data were analyzed by using three different methods of regression and these methods are compared. During these progress curve experiments, it was noticed that fructose 1,6-bisphosphate (Fru-P2) was not fully utilized in the presence of AMP. This anomaly could be best explained by proposing the formation of an AMP.Fur-P2 complex that was inactive with FBPase. Besides reducing the level of substrate available to FBPase, AMP caused slope-parabolic, intercept-parabolic noncompetitive inhibition with respect to Fru-P2. A kinetic model for AMP inhibition of the forward reaction of FBPase is presented. Initial rate kinetics were used to study the reverse reaction of FBPase; AMP was a slope-parabolic, intercept-parabolic noncompetitive inhibitor with respect to both fructose 6-phosphate and inorganic phosphate. Initial velocity experiments in which both fructose 6-phosphate and inorganic phosphate were varied were carried out in the absence and presence of AMP. The results of these experiments indicated to which reverse-reaction enzyme forms AMP was binding. The possible physiological significance of the AMP inhibition of FBPase and of the proposed AMP.Fru-P2 complex is discussed.
D000249:Adenosine Monophosphate / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D006597:Fructose-Bisphosphatase / Q000037:antagonists & inhibitors* / Q000302:isolation & purification; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008433:Mathematics
D000249:Adenosine Monophosphate; D006597:Fructose-Bisphosphatase