The citric acid cycle, also known as the Krebs cycle, is a fundamental metabolic pathway that takes place in the mitochondrial matrix. This cycle plays a crucial role in cellular respiration by oxidizing acetyl-CoA molecules derived from carbohydrates, fats, and proteins. The cycle produces carbon dioxide as a waste product and generates important energy carriers including NADH, FADH2, and ATP.
The citric acid cycle begins with the first step: the formation of citrate. In this reaction, acetyl-CoA, which contains two carbon atoms, combines with oxaloacetate, a four-carbon molecule. This condensation reaction is catalyzed by the enzyme citrate synthase and produces citrate, a six-carbon compound. This reaction is highly exergonic, meaning it releases energy, which helps drive the entire cycle forward.
The next crucial steps in the citric acid cycle involve two oxidative decarboxylation reactions. First, citrate is converted to isocitrate, then isocitrate undergoes oxidative decarboxylation to form alpha-ketoglutarate, releasing carbon dioxide and producing NADH. The second oxidative decarboxylation converts alpha-ketoglutarate to succinyl-CoA, again releasing CO2 and generating another NADH molecule. These reactions are significant because they remove carbon atoms from the cycle and capture energy in the form of NADH.
The final steps of the citric acid cycle focus on energy production and regeneration of oxaloacetate. Succinyl-CoA is converted to succinate, producing ATP or GTP through substrate-level phosphorylation. Succinate is then oxidized to fumarate, generating FADH2. Fumarate undergoes hydration to form malate, and finally, malate is oxidized to regenerate oxaloacetate while producing another NADH molecule. This regeneration of oxaloacetate allows the cycle to continue with new acetyl-CoA molecules.
In summary, each turn of the citric acid cycle completely oxidizes one acetyl-CoA molecule and produces significant energy carriers. The cycle generates three NADH molecules, one FADH2 molecule, and one ATP or GTP molecule directly. Additionally, two carbon dioxide molecules are released as waste products. The real energy payoff comes when NADH and FADH2 transfer their electrons to the electron transport chain, which ultimately produces approximately 30 ATP molecules per glucose molecule through oxidative phosphorylation.