The role of adenylate kinase in regulating the glycolysis rate and the potential contribution of the adenylate kinase reaction to ATP production were examined using mathematical models of energy metabolism in human erythrocytes and resting anaerobic mammalian skeletal muscle. The adenylate kinase reaction was shown to play a critical role in the regulation of cellular energy metabolism. Through the action of adenylate kinase, small changes in intracellular ATP give rise to large changes in AMP, a potent activator of glycolytic flux via the activation of phosphofructokinase (PFK). This mechanism ensures an increase in the glycolytic rate as ATP decreases within the physiological range of ATP concentrations. As a result, negative feedback regulation of glycolysis by ATP is established, allowing the rate of ATP production to adjust to the energy demands of the cell and thereby stabilizing ATP under varying rates of ATP consumption. Importantly, allosteric inhibition of PFK by ATP alone was insufficient to provide negative feedback regulation of glycolysis via ATP. The contribution of the adenylate kinase reaction to ATP production appears to be negligible. Also, due to the presence of adenylate kinase in cells, energy metabolism is regulated not by the absolute concentration of ATP, but by the energy charge or the ratio of ATP to the sum of ATP, ADP, and AMP.
Martinov et al. (Sun,) studied this question.