show that both enzyme-catalyzed reactions exhibit a substantial reduction in activation enthalpy, while the effect on activation entropy is relatively minor, demonstrating that enzyme-catalyzed chorismate mutase reactions are enthalpically-driven. Furthermore, we observe that the monofunctional chorismate mutase from B. subtilis more efficiently catalyzes this reaction than its promiscuous counterpart. This is supported by a structural analysis of the reaction pathway at the transition state, from which we identified key residues explaining the enthalpically-driven nature of the reactions, and also the difference in efficiencies between the two enzymes.