Metabolic potentials

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Hans V. Westerhoff

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Mar 6, 2026, 11:06:53 AM (11 days ago) Mar 6
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Dear colleagues,

Today a paper by >20 biochemical thermodynamics and myself came out with recommendations of the use of a 'reference metabolic potential' to replace the reference chemical potential in biochemistry.  It is a much further extension of the apparent chemical potential defined by Alberty (and Athel, Bob, Keith and myself). 
The reference metabolic potential corresponds to the reference Gibbs energy of formation from standard metabolic precursors at reference concentrations that make sense for (intracellular biochemistry).
This has a number of advantages, for instance meaningful metabolic landscapes, and positive metabolic potentials rather than the negative chemical potentials.

The metabolic potentials should be closer to the world view of the average biochemist ()and thereby more intuitive), i.e. to intracellular conditions, which are pretty similar across the biosphere of this planet.  


It also suggests  that there may be optimal standard conditions for kinetics and thermodynamics, but this may require more debate.

I attach the paper.

It may have some relevance for the openTECR group, so let me know if you are interested.  

--
With kind regards

Hans V. Westerhoff
Westerhoff et al FEBS J 100460585.pdf

Joana C. Xavier

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Mar 12, 2026, 10:53:21 AM (5 days ago) Mar 12
to openTECR: Open Database of Thermodynamics of Enzyme-Catalyzed Reactions
Dear Professor Westerhoff and colleagues,

Congratulations on a landmark paper. I will be recommending it to colleagues and students immediately.

A clarification: the metabolic reference state anchors water activity to osmolarity, which does not account for

1. macromolecular excluded volume (something others have tried to address e.g. Angeles-Martinez & Theodoropoulos, Biophys. J., 2015)
2. macromolecular hydration shells / bound water; this will have a non-negligible effect in water-consuming reactions

Do you anticipate future corrections addressing cytoplasmic crowding more directly?

I am also very eager to hear more on the debatable optimal standard conditions for kinetics and thermodynamics.

Thank you for your work and sharing it with the community here. 

Best wishes to all
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