FIGURE 12-16 The citric acid cycle. Acetyl CoA is metabolized to CO₂ and the high-energy electron carriers NADH and FADH₂. In reaction 1, a two-carbon acetyl residue from acetyl CoA condenses with the four-carbon molecule oxaloacetate to form the six-carbon citrate. In the remaining reactions (2–9), each molecule of citrate is eventually converted back to oxaloacetate, losing two CO₂ molecules in the process. In each turn of the cycle, four pairs of electrons are removed from carbon atoms, forming three molecules of NADH, one molecule of FADH₂, and one molecule of GTP. The two carbon atoms that enter the cycle with acetyl CoA are highlighted in blue through succinyl CoA. In succinate and fumarate, which are symmetric molecules, they can no longer be specifically denoted. Isotope-labeling studies have shown that these carbon atoms are not lost in the turn of the cycle in which they enter; on average, one will be lost as CO₂ during the next turn of the cycle and the other in subsequent turns.