Metabolic thermodynamics: pertinent reference state and energy potentials
Chemical potentials (molar Gibbs energies) are usually extrapolated to the remote physical–chemical reference state and then stored. Subsequent use under in vivo conditions requires a similarly substantial, reverse extrapolation, again with significant potential errors. In order to shrink both extrapolations drastically and thereby enhance both biological meaning and accuracy, we propose a transformation to a more biological reference state: pH = 7, pMg = 3, 99.5% water, with 1 m m each of the additional ‘precursors’ inorganic phosphate, sulfate, ammonium, and bicarbonate, and with twin temperatures 37 and 25 °C, ionic strength 0.15 m and m m as concentration unit. These precursors substitute for reference compounds alien to biology such as H 2 at 1 bar, and solid graphite, sulfur, and phosphorus. The standard chemical potentials are herewith increased by the magnitudes of the chemical potentials of protons, Mg 2+ , water, and the four precursors, each multiplied by the number of corresponding atoms in the molecule. This defines standard ‘metabolic potentials’. We make these potentials findable and accessible as 1360 collated standard chemical potentials for 320 compounds of biochemical interest at the twin metabolic reference states. We do this for 3 reference pH's: We present the metabolic reference state as a convenient anchor , not a universal intracellular milieu. All datasets must continue to report the actual experimental state ( T , pH, pMg, I , osmolarity, concentrations), yet aim at (also) reporting parameter values for this anchor state; we supply algorithms to transform between states. This preserves interoperability across diverse organelles, media and between enzymology and chemical engineering, while facilitating reuse.
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Westerhoff, H. V., Bakker, B. M., Bommarius, A. S., Cárdenas, M. L., CORNISH-BOWDEN, A., Fitzpatrick, P. F., Halling, P. J., Hatzimanikatis, V., Kettner, C., Liu, Y., McDonald, A. G., Noor, E., Pleiss, J., Raushel, F. M., Rohwer, J. M., Schnell, S., Kf, T., Tsai, von Stockar, U., et al. (2026). Metabolic thermodynamics: pertinent reference state and energy potentials. The FEBS Journal, Article febs.70415. https://doi.org/10.1111/febs.70415
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Netherlands Organisation for Applied Scientific Research
University Medical Center Groningen
Georgia Institute of Technology
Centre National de la Recherche Scientifique
Centre National de la Recherche Scientifique
The University of Texas Health Science Center at San Antonio
University of Strathclyde
École Polytechnique Fédérale de Lausanne
Beilstein-Institut
Netherlands Organisation for Applied Scientific Research
2026-03-05
febs.70415
REVIEWED
EPFL