The activation energy (or free energy of activation), abbreviated as E_a, is the small amount of energy input necessary for all chemical reactions to occur. During chemical reactions, certain chemical bonds break, and new ones form. For example, when a glucose molecule breaks down, bonds between the molecule's carbon atoms break. Since these are energy-storing bonds, they release energy when broken. However, the molecule must be somewhat contorted to get into a state that allows the bonds to break. A small energy input is required to achieve this high-energy, unstable state, called the transition state. For this reason, reactant molecules do not last long in their transition state but very quickly proceed to the chemical reaction's next steps. The reaction's transition state exists at a higher energy state than the reactants, and thus, E_a is always positive.

When an enzyme binds its substrate, it forms an enzyme-substrate complex. This complex lowers the reaction's activation energy and promotes its rapid progression in one of many ways. The enzyme-substrate complex can lower the activation energy by contorting substrate molecules in such a way as to facilitate bond-breaking, helping to reach the transition state. Enzymes can also lower activation energies by taking part in the chemical reaction. The amino acid residues can provide specific ions or chemical groups that form covalent bonds with substrate molecules as a necessary step in the reaction process. It is important to remember that the enzyme will always return to its original state at the reaction's completion. One of the hallmark properties of enzymes is that they remain ultimately unchanged by the reactions they catalyze. After an enzyme catalyzes a reaction, it releases its product(s).

This text is adapted from Openstax Biology 2e, Section 6.2 Potential, Kinetic, Free and Activation energy and Section 6.5: Enzymes,