Thermodynamics tells you whether a reaction can happen spontaneously. The key quantity is Gibbs free energy (G). A reaction is spontaneous if its ΔG is negative.
Free energy, coupling, and why ATP works
Bioenergetics
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Negative ΔG: spontaneous, releases energy Positive ΔG: needs to be paid for ATP, the currency The coupled result
Spontaneous does not mean fastΔG says whether a reaction can happen, not whether it will happen in your lifetime. Glucose burning in air is enormously spontaneous and completely stable on a table. Activation energy is what decides the rate, and enzymes only ever change that, never ΔG.
Why ATP is not a special bondThere is no unusual chemistry in the phosphoanhydride bond. Hydrolysis releases energy because the products are more stable: less charge repulsion between the phosphates, better resonance in free phosphate, and better solvation. ATP is unstable, not magic.
ΔG versus ΔG°′ΔG°′ is the standard value at 1 M, pH 7. ΔG is the actual value under the concentrations in the cell, and it is the one that decides direction. A reaction with positive ΔG°′ runs forward all day if the cell keeps the product concentration low.
The cell never breaks thermodynamics; it just does its accounting in pairs. An unfavorable reaction is run by physically joining it to a favorable one, so what the universe sees is a single reaction with a negative ΔG.
ΔG > 0 (endergonic): non-spontaneous as written (but can be driven by coupling).
ΔG = 0: equilibrium.
Magnitude of ΔG does NOT tell you how fast the reaction goes - only thermodynamics, not kinetics. Enzymes change the rate (by lowering activation energy) without changing ΔG.
ΔG vs. ΔG°’
ΔG°’: standard free energy change at physiologic conditions (pH 7, 1 M substrates). A property of the reaction.
ΔG: actual free energy change under cellular conditions. Depends on actual concentrations. What matters biologically.
A reaction with ΔG°’ > 0 can still have ΔG < 0 in a cell if substrate/product ratios favor forward flow.
ΔG=ΔG∘′+RTlnQ
where Q is the mass action ratio (products/substrates at the moment). Cells maintain non-equilibrium concentrations to keep metabolism flowing.
What does a negative ΔG indicate about a reaction?
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The reaction is exergonic - thermodynamically spontaneous as written. Energy is released, and the reaction proceeds toward products until equilibrium. Magnitude of ΔG does not say how fast the reaction runs; a catalyst (enzyme) is needed to achieve biologically useful rates.
How can a reaction with positive ΔG°’ still be favorable in the cell?
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Because ΔG depends on actual concentrations, not just ΔG°’. If the cell keeps product concentration low (by consuming it in the next step) or substrate concentration high, the mass action term (RT ln Q) can be strongly negative, making the actual ΔG negative. This is how unfavorable standard ΔG°’ reactions proceed in cells - through concentration control.
How do enzymes affect ΔG of a reaction?
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They do not. Enzymes lower the activation energy (Ea), speeding up the rate of both forward and reverse reactions. ΔG is determined only by the energy difference between reactants and products, which enzymes do not change. A reaction that is thermodynamically impossible stays impossible with or without an enzyme.
