Thermodynamically favourable?
A reaction only runs spontaneously if its Gibbs free energy change is negative. We measured a few everyday processes in our lab in Gothenburg.
| Process | ΔG | Verdict |
|---|---|---|
| Annotating a gene as “hypothetical protein” | ΔG ≪ 0 | The lowest-energy state of any genome. |
| Getting anything signed in Sweden in July | ΔG ≫ 0 | Inhibited by semester. Activity resumes in mid-August. |
| Friday afterwork | ΔG < 0 | Spontaneous. Reaction rate peaks at 17:00. |
| First FBA with a published model works | ΔG ≫ 0 | Thermodynamically forbidden. Check your units. |
| Engineered pathway reaches the predicted titer | ΔG ≫ 0 | Only proceeds when coupled to a PhD student. |
| Three biological replicates cluster together | ΔG ≈ 0 | Near equilibrium. Replicate 2 can go either way. |
| Proteomics detects your enzyme of interest | ΔG > 0 | Below detection limit. Always. |
| Gene set enrichment returns “response to stimulus” | ΔG ≪ 0 | Spontaneous. So does every other experiment. |
| Reviewer 2 accepts without comments | ΔG ≫ 0 | Not observed in vivo or in silico. |
| Pipeline runs on someone else's laptop | ΔG > 0 | High activation barrier: dependencies. |
| Cycling up Gibraltargatan to Chalmers in November rain | ΔG ≫ 0 | The steepest free-energy hill in Gothenburg. No coincidence that it starts with Gib(bs). |
| Västtrafik tram arrives exactly on time | ΔG ≈ 0 | Near equilibrium. Can go either way. |
| Re-running an old analysis exactly as published | ΔG > 0 | Effectively irreversible. Nobody remembers the parameters. |
The real story. The direction of a metabolic reaction is set by its Gibbs free energy change, ΔG = ΔG°′ + RT ln Q, which depends on both the reaction itself and the concentrations of its substrates and products. Reactions with ΔG < 0 can proceed forward; those with ΔG > 0 need to be coupled to an energy-releasing reaction, such as ATP hydrolysis.
Adding these thermodynamic constraints to metabolic models rules out impossible flux directions and makes predictions more realistic.