Citric acid cycle

The citric acid cycle—also known as the Krebs cycle, Szent–Györgyi–Krebs cycle or the TCA cycle (tricarboxylic acid cycle)^[1][2]—is a series of biochemical reactions to release the energy stored in nutrients through the oxidation of acetyl-CoA derived from carbohydrates, fats, and proteins. The chemical energy released is available under the form of ATP. The Krebs cycle is used by organisms that respire (as opposed to organisms that ferment) to generate energy, either by anaerobic respiration or aerobic respiration. In addition, the cycle provides precursors of certain amino acids, as well as the reducing agent NADH, that are used in numerous other reactions. Its central importance to many biochemical pathways suggests that it was one of the earliest components of metabolism.^[3][4] Even though it is branded as a "cycle", it is not necessary for metabolites to follow only one specific route; at least three alternative segments of the citric acid cycle have been recognized.^[5]

The name of this metabolic pathway is derived from the citric acid (a tricarboxylic acid, often called citrate, as the ionized form predominates at biological pH^[6]) that is consumed and then regenerated by this sequence of reactions to complete the cycle. The cycle consumes acetate (in the form of acetyl-CoA) and water, reduces NAD⁺ to NADH, releasing carbon dioxide. The NADH generated by the citric acid cycle is fed into the oxidative phosphorylation (electron transport) pathway. The net result of these two closely linked pathways is the oxidation of nutrients to produce usable chemical energy in the form of ATP.

In eukaryotic cells, the citric acid cycle occurs in the matrix of the mitochondrion. In prokaryotic cells, such as bacteria, which lack mitochondria, the citric acid cycle reaction sequence is performed in the cytosol with the proton gradient for ATP production being across the cell's surface (plasma membrane) rather than the inner membrane of the mitochondrion.

For each pyruvate molecule (from glycolysis), the overall yield of energy-containing compounds from the citric acid cycle is three NADH, one FADH₂, and one GTP.^[7]