Many processes in cells are energetically unfavorable (ΔG > 0) and will not proceed spontaneously. Examples include the synthesis of DNA from nucleotides and the transport of a substance across the plasma membrane from a lower to a higher concentration. Cells can carry out an energy-requiring, or endergonic, reaction (ΔG₁ > 0) by coupling it to an energy-releasing, or exergonic, reaction (ΔG₂ < 0) if the sum of the two reactions has an overall net negative ΔG.

Suppose, for example, that the reaction A ⇌ B + X has a ΔG of +5 kcal/mol and that the reaction X ⇌ Y + Z has a ΔG of –10 kcal/mol:

In the absence of the second reaction, there would be much more A than B at equilibrium. However, because the conversion of X to Y + Z is such a favorable reaction, it will pull the first process toward the formation of B and the consumption of A. Energetically unfavorable reactions in cells are often coupled to the energy-releasing hydrolysis of ATP.