The adenylate energy charge is an index used to measure the energy status of biological cells.

ATP or Mg-ATP is the principal molecule for storing and transferring energy in the cell : it is used for biosynthetic pathways, maintenance of transmembrane gradients, movement, cell division, etc... More than 90% of the ATP is produced by phosphorylation of ADP by the ATP synthase.[1] ATP can also be produced by “substrate level phosphorylation” reactions (ADP phosphorylation by (1,3)-bisphosphoglycerate, phosphoenolpyruvate, phosphocreatine), by the succinate-CoA ligase and phosphoenolpyruvate carboxylkinase, and by adenylate kinase, an enzyme that maintains the three adenine nucleotides in equilibrium ().

The energy charge is related to ATP, ADP and AMP concentrations. It was first defined by Atkinson and Walton who found that it was necessary to take into account the concentration of all three nucleotides, rather than just ATP and ADP, to account for the energy status in metabolism. Since the adenylate kinase maintains two ADP molecules in equilibrium with one ATP (), Atkinson defined the adenylate energy charge as:[2]

The energy charge of most cells varies between 0.7 and 0.95[1] - oscillations in this range are quite frequent. Daniel Atkinson showed that when the energy charge increases from 0.6 to 1.0, the citrate lyase and phosphoribosyl pyrophosphate synthetase, two enzymes controlling anabolic (ATP-demanding) pathways are activated,[2][3] while the phosphofructokinase and the pyruvate dehydrogenase, two enzymes controlling amphibolic pathways (supplying ATP as well as important biosynthetic intermediates) are inhibited[4] He concluded that control of these pathways has evolved to maintain the energy charge within rather narrow limits - in other words, that the energy charge, like the pH of a cell, must be buffered at all times. We now know that most if not all anabolic and catabolic pathways are indeed controlled, directly and indirectly, by the energy charge.[5][6][7] In addition to direct regulation of several enzymes by adenyl nucleotides, an AMP-activated protein kinase known as AMP-K phosphorylates and thereby regulates key enzymes when the energy charge decreases. This results in switching off anabolic pathways while switching on catabolic pathways when AMP increases.[8][9]

Life depends on an adequate energy charge. If ATP synthesis is momentarily insufficient to maintain an adequate energy charge, AMP can be converted by two different pathways to hypoxanthine and ribose-5P, followed by irreversible oxidation of hypoxanthine to uric acid. This helps to buffer the adenylate energy charge by decreasing the total {ATP+ADP+AMP} concentration.[10]

References

  1. ^ a b De la Fuente IM, Cortés JM, Valero E, Desroches M, Rodrigues S, Malaina I, Martínez L (2014). "On the dynamics of the adenylate energy system: homeorhesis vs homeostasis". PLOS ONE. 9 (10): e108676. Bibcode:2014PLoSO...9j8676D. doi:10.1371/journal.pone.0108676. PMC 4193753. PMID 25303477.
  2. ^ a b Atkinson DE, Walton GM (July 1967). "Adenosine triphosphate conservation in metabolic regulation. Rat liver citrate cleavage enzyme". The Journal of Biological Chemistry. 242 (13): 3239–41. doi:10.1016/S0021-9258(18)95956-9. PMID 6027798.
  3. ^ Atkinson DE, Walton GM (February 1965). "Kinetics of Regulatory Enzymes. Escherichia coli Phosphofructokinase". The Journal of Biological Chemistry. 240: 757–63. doi:10.1016/S0021-9258(17)45240-9. PMID 14275132.
  4. ^ Shen LC, Fall L, Walton GM, Atkinson DE (November 1968). "Interaction between energy charge and metabolite modulation in the regulation of enzymes of amphibolic sequences. Phosphofructokinase and pyruvate dehydrogenase". Biochemistry. 7 (11): 4041–5. doi:10.1021/bi00851a035. PMID 4301881.
  5. ^ Berg JM, Tymoczko JL, Gatto GJ, Stryer L (8 April 2015). Biochemistry (Eighth ed.). New York. ISBN 978-1-4641-2610-9. OCLC 913469736.((cite book)): CS1 maint: location missing publisher (link)
  6. ^ Nelson DL, Cox MM, Lehninger AL (January 2017). Lehninger principles of biochemistry (Seventh ed.). New York, NY. ISBN 978-1-4641-2611-6. OCLC 986827885.((cite book)): CS1 maint: location missing publisher (link)
  7. ^ Horton H R (2006). Principles of Biochemistry (4th ed.). Upper Saddle River, NJ: Pearson Prentice Hall. ISBN 978-0-13-145306-7. OCLC 58594968.
  8. ^ Ke R, Xu Q, Li C, Luo L, Huang D (April 2018). "Mechanisms of AMPK in the maintenance of ATP balance during energy metabolism". Cell Biology International. 42 (4): 384–392. doi:10.1002/cbin.10915. PMID 29205673.
  9. ^ Hardie DG (April 2015). "AMPK: positive and negative regulation, and its role in whole-body energy homeostasis". Current Opinion in Cell Biology. 33: 1–7. doi:10.1016/j.ceb.2014.09.004. PMID 25259783.
  10. ^ Chapman AG, Atkinson DE (December 1973). "Stabilization of adenylate energy charge by the adenylate deaminase reaction". The Journal of Biological Chemistry. 248 (23): 8309–12. doi:10.1016/S0021-9258(19)43229-8. PMID 4752956.


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