isocitrate

Meaning: Isocitrate is the isomer of citrate produced in step 2 of the citric acid cycle. Aconitase moves the hydroxyl group from a tertiary to a secondary carbon, so the molecule can then be oxidized. Isocitrate dehydrogenase then oxidizes it and removes a carboxyl group (oxidative decarboxylation), giving α-ketoglutarate (5 carbons), CO₂, and NADH. This is the first of two CO₂-releasing steps in the cycle (the second is α-ketoglutarate dehydrogenase).

Equation: isocitrate + NAD⁺ → α-ketoglutarate + CO₂ + NADH (catalyzed by isocitrate dehydrogenase; NAD⁺ and NADH are coenzymes measured in mol, and the reaction is written without H⁺ for simplicity).

On the MCAT: Expect questions on cycle order (citrate → isocitrate → α-ketoglutarate), counting carbons, or finding where CO₂ and NADH are made. Regulation is also tested: isocitrate dehydrogenase is inhibited by high ATP and NADH and activated by ADP, so a high energy charge slows the cycle. Passages may ask you to predict which intermediates build up if this enzyme is inhibited (isocitrate and citrate rise).

Common confusion: Students think isocitrate is a different compound from citrate with a different formula. It is an isomer with the same formula, and aconitase interconverts them. Another mistake is to link isocitrate to the glyoxylate cycle, which is a separate pathway in plants and bacteria that uses isocitrate lyase and is not the usual MCAT focus.