Energy consumption in a cyclic phosphorylation/dephosphorylation cascade.
Cyclic phosphorylation/dephosphorylation cascade systems are responsible for regulating numerous metabolic pathways. The capacity of a cyclic cascade system to maintain a steady-state level of phosphorylation and, hence, a specific biological activity of a phosphorylatable protein is dependent upon a constant supply of metabolic energy (ATP). Quantification of the extent of ATP consumption in a cyclic cascade was examined experimentally with the model in vitro phosphorylation/dephosphorylation system described in detail in the previous paper (Shacter, E., Chock, P. B., and Stadtman, E. R. (1984) J. Biol. Chem. 259, 12252-12259). The results indicate that (a) when the concentrations of converter enzymes and interconvertible substrate are held constant and the fractional phosphorylation of the substrate is varied by changing the allosteric effector concentrations, the rate of ATP consumption in the monocyclic cascade is directly proportional to the steady-state level of phosphorylation being maintained. (b) Attainment of a particular steady-state level of phosphorylation is determined by the net ratio of the protein kinase and phosphatase activities and is independent of the absolute concentrations of these enzymes. (c) Whereas the time required to reach a given steady state is inversely proportional to the converter enzyme concentrations, the amount of ATP consumed in maintaining that steady state is directly proportional to the kinase and phosphatase concentrations. In addition, a theoretical analysis based upon experimentally determined parameters for two in vivo cyclic cascade systems (pyruvate kinase and glycogen phosphorylase) revealed that under normal conditions, cyclic phosphorylation/dephosphorylation cascades consume only a small proportion (less than 0.02%) of the total cellular energy flux.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D002417:Cattle; D000242:Cyclic AMP / Q000378:metabolism; D004734:Energy Metabolism; D007700:Kinetics; D008954:Models, Biological; D009206:Myocardium / Q000201:enzymology; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D013997:Time Factors
D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D011494:Protein Kinases; D010749:Phosphoprotein Phosphatases