Living systems pay energetic costs that traditional mechanical physics does not account for. One clear example is the energy needed to keep certain biochemical processes running, such as those involved in photosynthesis, while actively preventing other chemical reactions from taking place. In classical mechanics, if nothing moves, no work is done, meaning there is no energy cost associated with stopping something from happening. However, more advanced thermodynamic calculations show that this assumption does not hold for living systems. These hidden costs are real and can be surprisingly large.

A new study published today (January 6) in the Journal of Statistical Mechanics: Theory and Experiment (JSTAT) introduces a thermodynamic framework that makes it possible to calculate these previously overlooked energy expenses. The approach offers a new way to understand how metabolic pathways were selected and refined during the earliest stages of life on Earth.

How Early Life Learned to Control Chemistry

Life likely began when simple organic molecules formed a boundary separating an interior from the surrounding environment. This first cell membrane created a clear distinction between inside and outside. From that point on, the system had to spend energy to maintain this separation and to limit which chemical reactions could occur internally. Instead of allowing every possible reaction, early cells selected only a small set of metabolic pathways that could use incoming materials from the "outside" to produce useful new compounds. The emergence of life was inseparable from this need to manage boundaries and choices.

While metabolism has obvious energy costs tied to chemical reactions themselves, there is also an additional cost associated with guiding chemical activity along specific pathways. This extra effort prevents reactions from branching into all other physically possible alternatives. From the perspective of classical mechanics, these boundary conditions and reaction constraints should not require energy, because they are treated as fixed and external. In reality, they contribute to entropy production and carry an energetic price.

A New Way to Measure Metabolic Efficiency

Praful Gagrani, a researcher at the University of Tokyo and lead author of the study, worked with colleagues Nino Lauber (University of Vienna), Eric Smith (Georgia Institute of Technology and Earth-Life Science Institute), and Christoph Flamm (University of Vienna) to develop a method for calculating these hidden costs. Their approach allows scientists to rank metabolic pathways based on how energetically demanding they are, offering valuable insight into biological efficiency and evolution.

"What inspired the new work is that Eric Smith, one of the co-authors, used MØD, a software developed by Flamm and co-workers, to enumerate all the possible pathways that can 'build' organic molecules starting from CO2."