Role of substrate inhibition kinetics in enzymatic chemical oscillations.
Two chemical kinetic models are investigated using standard nonlinear dynamics techniques to determine the conditions under which substrate inhibition kinetics can lead to oscillations. The first model is a classical substrate inhibition scheme based on Michaelis-Menten kinetics and involves a single substrate. Only when this reaction takes place in a flow reactor (i.e., both substrate and product are taken to follow reversible flow terms) are oscillations observed; however, the range of parameter values over which such oscillations occur is so narrow it is experimentally unobservable. A second model based on a general mechanism applied to the kinetics of many pH-dependent enzymes is also studied. This second model includes both substrate inhibition kinetics as well as autocatalysis through the activation of the enzyme by hydrogen ion. We find that it is the autocatalysis that is always responsible for oscillatory behavior in this scheme. The substrate inhibition terms affect the steady-state behavior but do not lead to oscillations unless product inhibition or multiple substrates are present; this is a general conclusion we can draw from our studies of both the classical substrate inhibition scheme and the pH-dependent enzyme mechanism. Finally, an analysis of the nullclines for these two models allows us to prove that the nullcline slopes must have a negative value for oscillatory behavior to exist; this proof can explain our results. From our analysis, we conclude with a brief discussion of other enzymes that might be expected to produce oscillatory behavior based on a pH-dependent substrate inhibition mechanism.
Shen
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P
Department of Chemistry, Indiana University Purdue University Indianapolis (IUPUI) 46202.
Larter
R
R
D000110:Acetylcholinesterase / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004798:Enzymes / Q000378:metabolism*; D007700:Kinetics; D008433:Mathematics; D008962:Models, Theoretical; D009991:Oscillometry
D002800:Cholinesterase Inhibitors; D004791:Enzyme Inhibitors; D004798:Enzymes; D000110:Acetylcholinesterase