  Adenosine 5'-triphosphate (ATP) is the nearly ubiquitous "energy currency" of
living organisms, and thus is a crucial participant in the majority of
enzymatic reactions. The standard models in enzyme kinetics generally ignore
the temporal dynamics of ATP because it is assumed to be present in large
excess. However, this assumption may not hold in many situations of cellular
stress where ATP concentrations may be comparable to substrate levels. Here, we
demonstrate the importance of ATP concentration on the dynamics of multi-enzyme
reactions by explicit consideration of ATP as a secondary substrate for an
enzyme. We apply our model to the mitogen-activated protein (MAP) kinase
cascade, which is involved in the regulation of a vast range of cellular
activities. We show that three fundamental features of this signaling network
--- (i) duration of response, (ii) signal amplification, and (iii)
ultrasensitivity to stimulus concentration --- are all dependent on ATP
concentration. Our results indicate that the concentration of ATP regulates the
response of the MAP kinase activation network, and potentially suggests another
possible mechanism for disruption of the cascade in pathogenic states.
