SUMMARY

• 19.1 The Citric Acid Cycle Consists of Two Stages

  The first stage of the citric acid cycle consists of the condensation of acetyl CoA with oxaloacetate, followed by two oxidative decarboxylations. In the second stage of the cycle, oxaloacetate is regenerated, coupled with the formation of high-transfer-potential electrons and a molecule of ATP.

• 19.2 Stage One Oxidizes Two Carbon Atoms to Gather Energy-Rich Electrons

  The cycle starts with the condensation of oxaloacetate (containing four carbon atoms, abbreviated as C₄) and acetyl CoA (C₂) to give citrate (C₆), which is isomerized to isocitrate (C₆). Oxidative decarboxylation of this intermediate gives α-ketoglutarate (C₅). The second molecule of carbon dioxide comes off in the next reaction, in which α-ketoglutarate is oxidatively decarboxylated to succinyl CoA (C₄).

• 19.3 Stage Two Regenerates Oxaloacetate and Harvests Energy-Rich Electrons

  The thioester of succinyl CoA is cleaved by orthophosphate to yield succinate, and a high-phosphoryl-transfer-potential compound in the form of ATP is concomitantly generated. Succinate is oxidized to fumarate (C₄), which is then hydrated to form malate (C₄). Finally, malate is oxidized to regenerate oxaloacetate (C₄). Thus, two carbon atoms from acetyl CoA enter the cycle, and two carbon atoms leave the cycle as CO₂ in the successive decarboxylations catalyzed by isocitrate dehydrogenase and α-ketoglutarate dehydrogenase. In the four oxidation–reduction reactions in the cycle, three pairs of electrons are transferred to NAD⁺ and one pair to FAD. These reduced electron carriers are subsequently oxidized by the electron-transport chain to generate approximately 9 molecules of ATP. In addition, 1 molecule of ATP is directly formed in the citric acid cycle. Hence, a total of 10 molecules of ATP are generated for each two-carbon fragment that is completely oxidized to H₂O and CO₂.

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• 19.4 The Citric Acid Cycle Is Regulated

  The citric acid cycle operates only under aerobic conditions because it requires a supply of NAD⁺ and FAD. The electron acceptors are regenerated when NADH and FADH₂ transfer their electrons to O₂ through the electrontransport chain, with the concomitant production of ATP. Consequently, the rate of the citric acid cycle depends on the need for ATP. In eukaryotes, the regulation of two enzymes in the cycle also is important for control. A high energy charge diminishes the activities of isocitrate dehydrogenase and α-ketoglutarate dehydrogenase. These mechanisms complement each other in reducing the rate of formation of acetyl CoA when the energy charge of the cell is high and when biosynthetic intermediates are abundant.

  When the cell has adequate energy available, the citric acid cycle can provide a source of building blocks for a host of important biomolecules, such as nucleotide bases, proteins, and heme groups. This use depletes the cycle of intermediates. When the cycle again needs to metabolize fuel, anaplerotic reactions replenish the cycle intermediates.

• 19.5 The Glyoxylate Cycle Enables Plants and Bacteria to Convert Fats into Carbohydrates

  The glyoxylate cycle enhances the metabolic versatility of many plants and bacteria. This cycle, which uses some of the reactions of the citric acid cycle, enables these organisms to convert fats into glucose. Two molecules of acetyl CoA are converted into succinate, which can be used to synthesize glucose.