In the course of one turn of the citric acid cycle, citrate is rearranged to isocitrate with little free energy change. Isocitrate is oxidized to a-ketoglutarate with the loss of one carbon as C0₂, and the energy from the oxidation is stored as NADH. Of the 109 kcal of energy released (per two isocitrates), 2 x 52.7 = 105.4 kcal are saved, an example of remarkably efficient coupling. This coupling is one of the main jobs of the enzyme controlling the reaction. There is nothing intrinsic in the chemistry to dictate that every time a molecule of isocitrate is oxidized to a-ketoglutarate, a molecule of NAD⁺ must be reduced to NADH. The free energy of the isocitrate oxidation could just as well be wasted as heat instead. The task of the enzyme is to make sure that when one reaction goes downhill, the other reaction goes uphill. Each step in the citric acid cycle is controlled by its own enzyme, which catalyzes that reaction and ensures the proper coupling to energy-storing processes.

a -Ketoglutarate next is oxidized to succinate in a process that resembles the oxidation of pyruvate to acetate, and the oxidation of G3P to DPG. The same pattern is followed: a-ketoglutarate is oxidized to succinate, part of the energy is stored in NADH, and part is saved temporarily by making a coenzyme A complex with the product. Succinyl coenzyme A then is broken down in the following step, with the formation of ATP. (Guanosine triphosphate, or GTP, actually is formed first, and then is used to make ATP.)