Journal of Molecular Evolution

, Volume 71, Issue 5–6, pp 346–355 | Cite as

Revisiting the Thermodynamic Theory of Optimal ATP Stoichiometries by Analysis of Various ATP-Producing Metabolic Pathways

  • Sarah Werner
  • Gabriele Diekert
  • Stefan SchusterEmail author


The stoichiometry of ATP-producing metabolic pathways had been analysed theoretically by several authors by using evolutionary arguments and optimality principles. Waddell et al. (Biochem Educ 27:12–13, 1999) analysed (lactate-producing) glycolysis and used linear irreversible thermodynamics. The result was that half of the free-energy difference should be converted into free-energy of ATP and the remaining half should be used to drive the pathway. The calculated stoichiometry is in agreement with the observed yield of two moles of ATP per mole of glucose. Using the same approach, we here analyse eight other metabolic pathways. Although the deviation is not very large, the calculated values do not fit as nicely as for glycolysis as leading to lactate. For example, for O2 respiration, the theoretical ATP yield equals 27.9. The real value varies among organisms between 26 and 38. For mixed-acid fermentation in Escherichia coli, the theoretical and experimental values are 2.24 and 2, respectively. For arginine degradation in M. pneumoniae, the calculated value is 2.43 mol of ATP, while in vivo only one mole is produced. During evolution, some pathways may not have reached their optimal ATP net production because energy yield is not their only function. Moreover, it should be acknowledged that the approach by linear irreversible thermodynamics is a rough approximation.


Arginine degradation ATP-producing metabolic pathway Entner–Doudoroff pathway Linear irreversible thermodynamics Mixed-acid fermentation Molar yield Optimal ATP stoichiometry Phosphoketolase pathway Respiratory pathway 



We thank Peter Ruoff (Stavanger, Norway) for very helpful suggestions. St. S. is very grateful to the late Reinhart Heinrich, who was his academic teacher and aroused his interest for optimality calculations. Financial support by the Deutsche Forschungsgemeinschaft within the framework of the Jena School of Microbial Communication is gratefully acknowledged.


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Copyright information

© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  • Sarah Werner
    • 1
  • Gabriele Diekert
    • 2
  • Stefan Schuster
    • 1
    Email author
  1. 1.Jena Centre for BioinformaticsFriedrich Schiller University JenaJenaGermany
  2. 2.Institute of MicrobiologyFriedrich Schiller University JenaJenaGermany

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