(tricarboxylic acid cycle, citric acid cycle, Krebs' cycle) A cyclic sequence of reactions, found almost universally in aerobic organisms, in which the acetyl portion of acetyl CoA is oxidized to carbon dioxide and hydrogen ions. The energy released by this oxidation is principally conserved by the concomitant reduction of NAD and flavoprotein. The reduced cofactors eventually provide energy for ATP formation via the *respiratory chain
and *oxidative phosphorylation
. Many different substrates can feed into the TCA cycle. Pyruvate, from the breakdown of glucose, feeds into the cycle by an oxidative decarboxylation to form acetyl CoA; the enzyme is the pyruvate dehydrogenase complex. The TCA cycle is not simply catabolic in function. It is in fact an amphibolic pathway, combining both anabolic and catabolic functions. The amino acids glutamate, aspartate, alanine, and glycine arise directly from the TCA cycle, while many other amino acids, the hexose and pentose sugars, the purines and pyrimidines, and the porphyrin-based molecules are indirectly formed from TCA cycle intermediates. Certain enzymatic reactions, termed anaplerotic reactions, produce TCA cycle intermediates to replace those removed by synthetic pathways. An example is the formation of oxaloacetate by the carboxylation of pyruvate.