The Citric Acid Cycle in Catabolism

The nutrients taken in by an organism can include large molecules. This observation is especially true in the case of animals, which ingest polysaccharides and proteins, which are polymers, as well as lipids. Nucleic acids constitute a very small percentage of the nutrients present in foodstuffs, and we shall not consider their catabolism. 

In Chapter 17, we discussed the glycolytic pathway by which sugars are converted to pyruvate, which then enters the citric acid cycle. In Chapter 21, we will see how fatty acids are converted to acetyl-CoA we learned about the fate of acetyl-CoA in the citric acid cycle earlier in this chapter. Amino acids enter the cycle by various paths. We will discuss catabolic reactions of amino acids in Chapter 23. 

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M Summarizethe role of the citric acid cycle In catabolism and anabolism. 

In summary, I have provided two examples of catabolic metabolic pathways linked to prodnction of ATP glycolysis, in which glucose is converted to lactate and pyrnvate and the citric acid cycle, in which acetate (derived from pyrnvate) is converted to carbon dioxide and water. In fact, these and other catabolic pathways generate more molecnles of ATP than 1 have so far let on. Now we need to do two things qnantitate the actnal yields of ATP and say something about how they are created. We begin by directing attention to the mitochondria. 

The pathways of amino acid catabolism are quite similar in most organisms. The focus of this chapter is on the pathways in vertebrates, because these have received the most research attention. As in carbohydrate and fatty acid catabolism, the processes of amino acid degradation converge on the central catabolic pathways, with the carbon skeletons of most amino acids finding their way to the citric acid cycle. In some cases the reaction pathways of amino acid breakdown closely parallel steps in the catabolism of fatty acids (Chapter 17). 

A second competitive pathway for the disposal of PA requires the initial conversion of PA into tyrosine. This reaction is catalyzed by the enzyme PAH (phenylalanine-4-monooxygenase EC 1.14.16.1). The resulting tyrosine molecule can then be catabolized into fumarate and ace-toacetate. Both products are nontoxic and can be further catabolized in the citric acid cycle. In Mrs. Urick and the majority of individuals suffering from HPA and PKU, there is a defect in the PAH enzyme system (NIH Consensus State-... 

However, the role of the citric acid cycle in cellular metabolism involves more than just catabolism. It plays a key role in anabolism, or bios)mthesis, as well. Figure 22.13 shows the central role of glycolysis and the citric acid cycle as energyharvesting reactions, as well as their role as a source of bios)mthetic precursors. 

FIGURE 19.1 The central relationship of the citric acid cycle to catabolism. Amino acids, fatty acids, and glucose can all produce acetyl-CoAin stage 1 of catabolism. In stage 2, acetyl-CoA enters the citric acid cycle. Stages 1 and 2 produce reduced electron carriers (shown here as e"). In stage 3, the electrons enter the electron transport chain, which then produces ATP. 

The central role of the citric acid cycle in metabolism The citric acid cycle plays a central role in metabolism. It is the first part of aerobic metabolism it is also amphibolic (both catabolic and anabolic). 

The third stage of catabolism is the citric acid cycle. In this cycle, the acetyl group of each molecule of acetyl-CoA is converted to two molecules of CO2. 

The combustion of the acetyl groups of acetyl-CoA by the citric acid cycle and oxidative phosphorylation to produce COg and HgO represents stage 3 of catabolism. The end products of the citric acid cycle, COg and HgO, are the ultimate waste products of aerobic catabolism. As we shall see in Chapter 20, the oxidation of acetyl-CoA during stage 3 metabolism generates most of the energy produced by the cell. 

Certain of the central pathways of intermediary metabolism, such as the citric acid cycle, and many metabolites of other pathways have dual purposes—they serve in both catabolism and anabolism. This dual nature is reflected in the designation of such pathways as amphibolic rather than solely catabolic or anabolic. In any event, in contrast to catabolism—which converges to the common intermediate, acetyl-CoA—the pathways of anabolism diverge from a small group of simple metabolic intermediates to yield a spectacular variety of cellular constituents. 

The next steps of glucose catabolism are called the citric acid cycle. The pyruvic acid formed in glycolysis is transported into the mitochondria, which arc subcellular organelles with double (inner and outer) membranes. They are referred to as the powerhous-... 

Figure 29.1 An overview of catabolic pathways for the degradation of food and the production of biochemical energy. The ultimate products of food catabolism are C02 and H2O, with the energy released in the citric acid cycle used to drive the endergonic synthesis of adenosine triphosphate (ATP) from adenosine diphosphate (ADP) plus phosphate ion, HOPO32-.

The conversion occurs through a multistep sequence of reactions catalyzed by a complex of enzymes and cofactors called the pyruvate dehydrogenase complex. The process occurs in three stages, each catalyzed by one of the enzymes in the complex, as outlined in Figure 29.11 on page 1152. Acetyl CoA, the ultimate product, then acts as fuel for the final stage of catabolism, the citric acid cycle. All the steps have laboratory analogies. 

The initial stages of catabolism result in the conversion of both fats and carbohydrates into acetyl groups that are bonded through a thioester link to coenzyme A. Acetyl CoA then enters the next stage of catabolism—the citric acid cycle, also called the tricarboxylic acid (TCA) cycle, or Krebs tycle, after Hans Krebs, who unraveled its complexities in 1937. The overall result of the cycle is the conversion of an acetyl group into two molecules of C02 plus reduced coenzymes by the eight-step sequence of reactions shown in Figure 29.12. 

Figure 15-1. Outline of the pathways for the catabolism of dietary carbohydrate, protein, and fat. All the pathways lead to the production of acetyl-CoA, which is oxidized in the citric acid cycle, ultimately yielding ATP in the process of oxidative phosphorylation.

Figure 16-2. The citric acid cycle the major catabolic pathway for acetyl-CoA in aerobic organisms. Acetyl-CoA, the product of carbohydrate, protein, and lipid catabolism, is taken into the cycle, together with HjO, and oxidized to CO2 with the release of reducing equivalents (2H). Subsequent oxidation of 2H in the respiratory chain leads to coupled phosphorylation of ADP to ATP. For one turn of the cycle, 11 are generated via oxidative phosphorylation and one arises at substrate level from the conversion of succinyl-CoA to succinate.

The citric acid cycle is at the heart of aerobic cellular metabolism, or respiration. This is true of both prokaryotic and eukaryotic organisms, of plants and animals, of organisms large and small. Here is the main point. On the one hand, the small molecule products of catabolism of carbohydrates, lipids, and amino acids feed into the citric acid cycle. There they are converted to the ultimate end products of catabolism, carbon dioxide and water. On the other hand, the molecules of the citric acid cycle are intermediates for carbohydrate, lipid, and amino acid synthesis. Thus, the citric acid cycle is said to be amphibolic, involved in both catabolism and anabolism. It is a sink for the products of degradation of carbohydrates, lipids, and proteins and a source of building blocks for them as well. 

The citric acid cycle is a catabolic, energy-generating metabolic pathway that is found enormously commonly in living nature. 

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