The Krebs cycle or tricarboxylic acid cycle (TCA) is a central part of aerobic respiration. During this cycle, the remaining carbon atoms from glucose are oxidized to CO2, and the electrons stripped from these oxidized carbons pass into the electron transport chain (ETC). The oxidation steps in the TCA generate most of the CO2 you exhale.
Initial Steps
The first step in the TCA involves two reactants -- a four-carbon molecule called oxaloacetate and another molecule called acetyl-CoA. Acetyl-CoA is a bulky coenzyme called CoA with a two-carbon group called an acetyl group stuck onto the end. An enzyme called citrate synthase transfers the acetyl group from acetyl-CoA to oxaloacetate to make six-carbon citrate. This step is highly exergonic -- in other words, it releases a lot of energy, so it's essentially irreversible. The citrate it generates is converted to isocitrate in a reversible reaction catalyzed by the enzyme aconitase.
Oxidation
Next, another enzyme called isocitrate dehydrogenase catalyzes a reaction that transfers a hydrogen atom with two electrons (a "hydride ion") from isocitrate to NAD+, making alpha-ketoglutarate and NADH. Isocitrate loses a carbon and two oxygens as CO2 in the process. This step is also highly exergonic. Alpha-ketoglutarate is oxidized in turn by the alpha-ketoglutarate dehydrogenase complex, which also adds a CoA to make succinyl-CoA. This reaction releases another molecule of CO2 and transfers a hydride ion to NAD+, making another NADH.
Oxaloacetate
The remaining steps in the cycle are all essentially reversible. Succinyl-CoA is converted to succinate by the enzyme succinyl-CoA synthetase, releasing CoA and producing a molecule of GTP as a byproduct. Next, the enzyme succinate dehydrogenase oxidizes succinate to fumarate and shunts the two electrons gained thereby into the ETC. The enzyme fumarase hydrates fumarate to make malate, and malate is oxidized to oxaloacetate in one final oxidation step. Like the first two oxidation steps, this last one also produces a molecule of NADH.
Function
The TCA produces three NADH for each turn of the cycle; these NADH pass the electrons they have gained off to the ETC. The ETC in turn transfers the electrons to a series of electron carriers and enzyme complexes, using the energy released by these transfers to pump hydrogen ions and create an electrochemical gradient across the membrane. Oxygen molecules await at the last complex in the ETC, where they will play their part as the final electron acceptor in the chain and become reduced to form water. The TCA is critical to this process because it supplies electrons to the ETC via the four oxidation reactions in the cycle.
References
- "Lehninger Principles of Biochemistry"; David L. Nelson, et al.; 2008
- "Biology"; Neil A. Campbell, et al.; 2008
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