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Berg JM, Tymoczko JL, Stryer L. Biochemistry. 5th edition. New York: W H Freeman; 2002.

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Biochemistry. 5th edition.

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Chapter 17The Citric Acid Cycle

Roundabouts, or traffic circles, function as hubs to facilitate traffic flow.


Roundabouts, or traffic circles, function as hubs to facilitate traffic flow. The citric acid cycle is the biochemical hub of the cell, oxidizing carbon fuels, usually in the form of acetyl CoA, as well as serving as a source of precursors for biosynthesis. (more...)

From Chapter 16, we know that glucose can be metabolized to pyruvate anaerobically to synthesize ATP through the glycolytic pathway. Glycolysis, however, harvests but a fraction of the ATP available from glucose. We now begin an exploration of the aerobic processing of glucose, which is the source of most of the ATP generated in metabolism. The aerobic processing of glucose starts with the complete oxidation of glucose derivatives to carbon dioxide. This oxidation takes place in the citric acid cycle, a series of reactions also known as the tricarboxylic acid (TCA) cycle or the Krebs cycle. The citric acid cycle is the final common pathway for the oxidation of fuel molecules—amino acids, fatty acids, and carbohydrates. Most fuel molecules enter the cycle as acetyl coenzyme A.

Image ch17fu2.jpg

Under aerobic conditions, the pyruvate generated from glucose is oxidatively decarboxylated to form acetyl CoA. In eukaryotes, the reactions of the citric acid cycle take place inside mitochondria, in contrast with those of glycolysis, which take place in the cytosol (Figure 17.1).

Figure 17.1. Mitochondrion.

Figure 17.1

Mitochondrion. The double membrane of the mitochondrion is evident in this electron micrograph. The numerous invaginations of the inner mitochondrial membrane are called cristae. The oxidative decarboxylation of pyruvate and the sequence of reactions (more...)

17.0.1. An Overview of the Citric Acid Cycle:

The citric acid cycle is the central metabolic hub of the cell. It is the gateway to the aerobic metabolism of any molecule that can be transformed into an acetyl group or dicarboxylic acid. The cycle is also an important source of precursors, not only for the storage forms of fuels, but also for the building blocks of many other molecules such as amino acids, nucleotide bases, cholesterol, and porphyrin (the organic component of heme).

What is the function of the citric acid cycle in transforming fuel molecules into ATP? Recall that fuel molecules are carbon compounds that are capable of being oxidized—of losing electrons (Chapter 14). The citric acid cycle includes a series of oxidation-reduction reactions that result in the oxidation of an acetyl group to two molecules of carbon dioxide.

The overall pattern of the citric acid cycle is shown in Figure 17.2. A four- carbon compound (oxaloacetate) condenses with a two-carbon acetyl unit to yield a six-carbon tricarboxylic acid (citrate). An isomer of citrate is then oxidatively decarboxylated. The resulting five-carbon compound (α-ketoglutarate) also is oxidatively decarboxylated to yield a four-carbon compound (succinate). Oxaloacetate is then regenerated from succinate. Two carbon atoms enter the cycle as an acetyl unit and two carbon atoms leave the cycle in the form of two molecules of carbon dioxide. Three hydride ions (hence, six electrons) are transferred to three molecules of nicotinamide adenine dinucleotide (NAD+), whereas one pair of hydrogen atoms (hence, two electrons) is transferred to one molecule of flavin adenine dinucleotide (FAD). The function of the citric acid cycle is the harvesting of high-energy electrons from carbon fuels. Note that the citric acid cycle itself neither generates a large amount of ATP nor includes oxygen as a reactant (Figure 17.3). Instead, the citric acid cycle removes electrons from acetyl CoA and uses these electrons to form NADH and FADH2. In oxidative phosphorylation (Chapter 18), electrons released in the reoxidation of NADH and FADH2 flow through a series of membrane proteins (referred to as the electron-transport chain) to generate a proton gradient across the membrane. These protons then flow through ATP synthase to generate ATP from ADP and inorganic phosphate. Oxygen is required for the citric acid cycle indirectly inasmuch as it is the electron acceptor at the end of the electron-transport chain, necessary to regenerate NAD+ and FAD.

Figure 17.2. Overview of the Citric Acid Cycle.

Figure 17.2

Overview of the Citric Acid Cycle. The citric acid cycle oxidizes two-carbon units, producing two molecules of CO2, one molecule of GTP, and high-energy electrons in the form of NADH and FADH2.

Figure 17.3. Cellular Respiration.

Figure 17.3

Cellular Respiration. The citric acid cycle constitutes the first stage in cellular respiration, the removal of high-energy electrons from carbon fuels (left). These electrons reduce O2 to generate a proton gradient (middle), which is used to synthesize (more...)

The citric acid cycle, in conjunction with oxidative phosphorylation, provides the vast majority of energy used by aerobic cells—in human beings, greater than 95%. It is highly efficient because a limited number of molecules can generate large amounts of NADH and FADH2. Note in Figure 17.2 that the four-carbon molecule, oxaloacetate, that initiates the first step in the citric acid cycle is regenerated at the end of one passage through the cycle. The oxaloacetate acts catalytically: it participates in the oxidation of the acetyl group but is itself regenerated. Thus, one molecule of oxaloacetate is capable of participating in the oxidation of many acetyl molecules.


17.1 The Citric Acid Cycle Oxidizes Two-Carbon Units

17.2 Entry to the Citric Acid Cycle and Metabolism Through It Are Controlled

17.3 The Citric Acid Cycle Is a Source of Biosynthetic Precursors

17.4 The Glyoxylate Cycle Enables Plants and Bacteria to Grow on Acetate



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Copyright © 2002, W. H. Freeman and Company.
Bookshelf ID: NBK21163


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