KREBS CYCLE

series of chemical reactions carried out in the living cell; in most higher animals, including humans, it is essential for the oxidative metabolism of glucose and other simple sugars. The breakdown of glucose to carbon dioxide and water is a complex set of chemical interconversions called carbohydrate catabolism, and the Krebs cycle is the second of three major stages in the process, occurring between glycolysis and oxidative phosphorylation. This cycle, also known as the citric acid cycle, was named in recognition of the German chemist Hans Krebs, whose research into the cellular utilization of glucose contributed greatly to the modern understanding of this aspect of metabolism. The name citric acid cycle is derived from the first product generated by the sequence of conversions, i.e., citric acid. The reactions are seen to comprise a cycle inasmuch as citric acid is both the first product and the final reactant, being regenerated at the conclusion of one complete set of chemical rearrangements. Citric acid is a so-called tricarboxylic acid, containing three carboxyl groups (COOH). Hence the Krebs cycle is sometimes referred to as the tricarboxylic acid (TCA) cycle. The Krebs cycle begins with the condensation of one molecule of a compound called oxaloacetic acid and one molecule of acetyl CoA (a derivative of coenzyme A; see coenzyme). The acetyl portion of acetyl CoA is derived from pyruvic acid, which is produced by the degradation of glucose in glycolysis. After condensation, the oxaloacetic acid and acetyl CoA react to produce citric acid, which serves as a substrate for seven distinct enzyme-catalyzed reactions that occur in sequence and proceed with the formation of seven intermediate compounds, including succinic acid, fumaric acid, and malic acid. Malic acid is converted to oxaloacetic acid, which, in turn, reacts with yet another molecule of acetyl CoA, thus producing citric acid, and the cycle begins again. Each turn of the citric acid cycle produces, simultaneously, two molecules of carbon dioxide and eight atoms of hydrogen as byproducts. The carbon dioxide generated is an ultimate end product of glucose breakdown and is removed from the cell by the blood. The hydrogen atoms are donated as hydride ions to the system of electron transport molecules, which allow for oxidative phosphorylation. In most higher plants, in certain microorganisms, such as the bacterium Escherichia coli, and in the algae, the citric acid cycle is modified to a form called the glyoxylate cycle, so named because of the prominent intermediate, glyoxylic acid.

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