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Download 17 The Citric Acid Cycle: The latabolism of Acetyl
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The Citric Acid Cycle: The latabolism of Acetyl-CoA 17 3fer A Mayes, PhD, DSc TRODUCTION Acetyl-CoA (C2) CoA The citric acid cycle (Krebs cycle, tricarboxylic d cycle) is a series of reactions in mitochondria that ing about the catabolism of acetyl residues, liberat; hydrogen equivalents, which, upon oxidation, ito the release of most of the free energy of tissue Is. The acetyl residues are in the form of acetyli(CH3-CO~S-CoA, active acetate), an ester of izyme A. Co A contains the vitamin panto thenic Citrate (C6) Oxaloacetate (C4) MEDICAL IMPORTANCE I The major function of the citric acid cycle is to act I the final common pathway for the oxidation of carihydrate, lipids, and protein, since glucose, fatty Is, and many amino acids are all metabolized to tylCoA or intermediates of the cycle. It also plays |major role in gluconeogenesis, transamination, mination, and lipogenesis. While several of these :esses are carried out in most tissues, the liver is {only tissue in which all occur. The repercussions |therefore profound when, for example, large num-s of hepatic cells are damaged or replaced by con-ctive tissue, as in acute hepatitis and cirrhosis, re-j|vdy. A mute testimony to the vital importance |citric acid cycle is the fact that very few if any ; abnormalities of its enzymes have been re-Jin humans; such abnormalities are presumably latible with normal development. C02 CO2 Figure 1 7 - 1 . Citric acid cycle, illustrating the catalytic role of oxaloacetate. generated (Fig 17-1). Since only a small quantity of oxaloacetate is needed to facilitate the conversion of a large quantity of acetyl units to CC>2, oxaloacetate may be considered to play a catalytic role. The ckric acid cycle is the mechanism by which much of the free energy liberated during the oxidation of carbohydrate, lipids, and amino acids is made available. During the course of oxidation of acetyl-CoA in the cycle, reducing equivalents in the form of hydrogen or of electrons are formed as a result of the activity of specific dehydrogenases. These reducing equivalents then enter the respiratory chain, where large amounts of ATP are generated in the process of oxidative phosphorylation (Fig 17-2; see also Chapter 13). The enzymes of the citric acid cycle are located in the mitochondrial matrix, either free or attached to the inner surface of the inner mitochondrial membrane, which facilitates the transfer of reducing equivalents to the adjacent enzymes of the respiratory chain, situated in the inner mitochondrial membrane. BOLIC ROLE OF THE I ACID CYCLE mtially, the cycle comprises the combination of ule of acetyl-CoA with the 4-carbon dicar-: acid oxaloacetate, resulting in the formation on tricarboxylic acid, citrate. There fol-[ series of reactions in the course of which 2 pies of C02 are released and oxaloacetate is re149