Reactions with ΔG < 0 (exergonic) release free energy and can happen on their own; ΔG > 0 (endergonic) need an input. Cells couple endergonic steps to ATP hydrolysis so the total ΔG is negative.
You know from ATP that cells spend ATP to do work, and from Exothermic and Endothermic Reactions that reactions can release or absorb heat. Biologists need one more idea to say whether a reaction can go at all: free energy, the energy available to do work.
🔑 Key idea
The change in free energy, $\Delta G$, tells whether a reaction can happen on its own. $\Delta G < 0$: exergonic, releases free energy, can proceed by itself. $\Delta G > 0$: endergonic, needs an input of free energy. Cells drive endergonic steps by coupling them to ATP hydrolysis, so the total $\Delta G$ is negative.
Free energy combines heat and order: $$\Delta G = \Delta H - T\Delta S$$ where $\Delta H$ is the change in enthalpy (heat content), $T$ the temperature in kelvin and $\Delta S$ the change in entropy (disorder). Breaking a big molecule into small ones usually gives off heat and increases disorder, so it tends to be exergonic. Building big molecules from small ones tends to be endergonic.
💡 Why it works
Why can coupling work? Free energy changes add. If making a molecule costs $+3.4$ kcal/mol and splitting ATP releases $7.3$ kcal/mol, an enzyme that joins the two into one process gives a total of $3.4 - 7.3 = -3.9$ kcal/mol. The cell does not "use heat" from ATP. Instead, the enzyme usually moves ATP's phosphate group onto the reactant, making a less stable intermediate that then reacts downhill.
An enzyme lowers the activation energy (the hill), but the start and end levels, and so ΔG, stay the same.
Worked examples
✏️ Worked example: Exergonic or endergonic?
Building sucrose from glucose and fructose has $\Delta G = +5.5$ kcal/mol. Breaking sucrose down has $\Delta G = -5.5$ kcal/mol. Which is exergonic?
A negative $\Delta G$ means free energy is released.
Breaking sucrose down is exergonic; building it is endergonic.
The two values are equal and opposite: running a reaction backward flips the sign.
Answer: Breaking sucrose down is exergonic.
✏️ Worked example: Coupling to ATP
Glutamic acid + ammonia → glutamine has $\Delta G = +3.4$ kcal/mol. ATP hydrolysis has $\Delta G = -7.3$ kcal/mol. What is the $\Delta G$ of the coupled process?
Add the two: $+3.4 + (-7.3) = -3.9$ kcal/mol.
The total is negative.
Answer: $\Delta G = -3.9$ kcal/mol, so the coupled process can go.
Free energy changes add: an uphill step plus a bigger downhill step gives a downhill total.
⚠️ Common mistake
Thinking "spontaneous" means "fast". $\Delta G$ says whether a reaction can go, not how quickly. Glucose and oxygen react with a large negative $\Delta G$, yet a sugar cube sits in the air for years, because the activation energy is high. Enzymes lower the activation energy and change the rate; they never change $\Delta G$.
The value $-7.3$ kcal/mol ($-30.5$ kJ/mol) is for standard conditions. In a living cell, where ATP is kept far more concentrated than ADP, splitting ATP releases even more free energy.
Practice
Pass with 3 right answers, the last 2 in a row. Each right answer earns 3 XP.