The citric acid cycle, which is also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle, is a collection of 9 enzyme-catalyzed chemical reactions that occurs in all living cells undergoing aerobic respiration. The citric acid cycle itself was officially identified in 1937 by Hans Adolf Krebs, who received the Nobel Prize for this discovery in 1953. In eukaryotes, the citric acid cycle occurs in the mitochondria. In prokaryotes, the TCA cycle occurs in the cytoplasm. The TCA cycle starts with acetyl-CoA, which is the “fuel” for the entire cycle. This important molecule is formed from the breakdown of glycogen (a stored form of glucose), fats, and many amino acids. At the start of the cycle, acetyl-CoA first transfers its 2-carbon acetyl group to the 4-carbon acceptor compound called oxaloacetate to form the 6-carbon compound (citrate) for which the cycle is named. The resulting citrate molecule then goes through a series of chemical transformations, whereby it loses one carboxyl group (leading to the 5-carbon compound called alpha-ketoglutarate) and then a second carboxyl group (leading to the 4-carbon compound called succinate). Succinate molecule is further oxidized to fumarate, then malate and finally oxaloacetate. The regeneration of the 4-carbon oxaloacetate, allows the TCA cycle to continue. Most of the energy generated by the oxidation steps in the TCA cycle is transferred as energy-rich electrons to NAD+, forming NADH. For each acetyl group that enters the citric acid cycle, three molecules of NADH are produced.

TCA Cycle References