Oxidative decarboxylation of isocitrate in TCA

Isocitrate dehydrogenase catalyzes the irreversible oxidative decarboxylation of isocitrate to α-ketoglutarate, yielding the first of three NADH molecules produced by the cycle and the first release of CO2 (Fig. 1). This is one of the rate-limiting steps of the TCA cycle.

The enzyme is allosterically activated by ADP (a low-energy signal) and Ca²⁺ and is inhibited by ATP and NADH, levels of which are elevated when the cell has abundant energy stores.

Figure 1: Formation of α-ketoglutarate from acetyl coenzyme A (CoA) and oxaloacetate. NAD(H) = nicotinamide adenine dinucleotide; CO2 = carbon dioxide.