The Citric Acid Cycle in Anabolism

All metabolic pathways are related, and all of them operate simultaneously. 

In catabolic pathways, nutrients, many of which are macromolecules, are broken down to smaller molecules, such as sugars, fatty acids, and amino acids. 

Small molecules are processed further, and the end products of catabolism frequently enter the citric acid cycle, which plays a key role in metabolism. 

The citric acid cycle is a source of starting materials for the biosynthesis of many important biomolecules, but the supply of the starting materials that are components of the cycle must be replenished if the cycle is to continue operating. See the Biochemical Connections box on page 569. In particular, the oxaloacetate in an organism must be maintained at a level sufficient to allow acetyl-CoA to enter the cycle. A reaction that replenishes a citric acid cycle intermediate is called an anaplerotic reaction. In some organisms, acetyl-CoA can be converted to oxaloacetate and other citric acid cycle intermediates by the glyoxylate cycle (Section 19.6), but mammals cannot do this. In mammals. 

Gluconeogenesis has many steps in common with the production of glucose in photosynthesis, but photosynthesis also has many reactions in common with the pentose phosphate pathway. Thus, nature has evolved common strategies to deal with carbohydrate metabolism in all its aspects. 

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FIGURE 16-15 Role of the citric acid cycle in anabolism. 

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. 

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). 

How is amino acid metabolism related to the citric acid cycle In addition, most of the intermediates have anabolic pathways leading to amino acids and fatty acids, as well as some that lead to porphyrins or pyrimidines. 

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 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 amphibolic, serving in both catabolism and anabolism cycle intermediates can be drawn off and used as the starting material for a variety of biosynthetic products. 

Figure 4 summarizes the result of these experiments. All reactions associated with carbohydrate metabolism are decreased by exposure to radiation, while all associated with the citric acid cycle and acetate catabolism are increased. Also, in every case studied, anabolic reactions were reduced by radiation. 

The catabolic and anabolic pathways that are responsible for the formation of many of the biomarker compounds discussed in this chapter occur through an intermediary metabolism via glycolysis and the citric acid cycle (Voet and Voet, 2004). The biosynthetic pathways of these compounds can be divided into primary and secondary metabolism (figure 9.4). Many of these compounds are not used as chemical biomarkers in estuarine research but are shown here simply to illustrate their relationship with the biomarkers discussed in this chapter. For more details on the biosynthetic pathways illustrated here, please refer to Voet and Voet (2004) and Engel and Macko (1993). 

Alcohol in the systemic circulation is oxidised in the liver principally (90%) by alcohol dehydrogenase to acetaldehyde and then by aldehyde dehydrogenase to products that enter the citric acid cycle or are utilised in various anabolic reactions. Other alcohol-metabolising enz Tnes are microsomal cytochrome P450 2E1 (which is also induced by alcohol) and catalase. 

Normally, 90-98% of the ethanol that enters the body is completely oxidized, predominantly in the liver, eventually entering the citric acid cycle or utilized in anabolic synthetic pathways. The kidney and lungs excrete only 5-10% of an absorbed dose unchanged. The rate of ethanol metabolism varies between individuals, by age, and may be under genetic control. 

Long-chain fatty acyl-CoA is at a crossroad of various metabolic pathways. Inside the mitochondrial matrix, fatty acyl-CoA is converted to acetyl-CoA, a compound that serves as substrate for aerobic energy production by concerted action of enzymes of the citric acid cycle and respiratory chain, and as precursor for ketone-body formation. The latter process is confined to the liver. The fatty acyl residue of acyl-CoA can also be incorporated into triacylglycerols and phospholipids (Figure 3). These anabolic processes occur in the extramitochondrial cytoplasmic space (see below). 

Amphibolic pathways can function in both anabolic and catabolic processes. The citric acid cycle is obviously catabolic, because acetyl groups are oxidized to form C02 and energy is conserved in reduced coenzyme molecules. The citric acid cycle is also anabolic, because several citric acid cycle intermediates are precursors in biosynthetic pathways (Figure 9.10). For example,... 

The citric acid cycle operates in both anabolic processes (e.g., the synthesis of fatty acids, cholesterol, heme, and glucose) and catabolic processes (e.g., amino acid degradation and energy production). 

Clearly, the reactions of glycolysis and the citric acid cycle are central to both anabolic and catabolic cellular activities. Metabolic pathways that function in both anabolism and catabolism are called amphibolic pathways. Consider for a moment the difficulties that the dual nature of these pathways could present to the cell. When the cell is actively growing, there is a great demand for biosynthetic precursors to build new cell structures. A close look at Figure 22.13 shows us that periods of active cell growth and biosynthesis may deplete the supply of citric acid cycle intermediates. The problem is, the processes of growth and biosynthesis also require a great deal of ATP ... 

In addition to its role in catabolism, the citric acid cycle also plays an important role in cellular anabolism, or biosynthetic reactions. Many of the citric acid cycle intermediates are precursors for the s)mthesis of amino acids and macromolecules required by the cell. A pathway that functions in both catabolic and anabolic reactions is called an amphibolic pathway. 

How does the reaction described in Problem 22.75 allow the citric acid cycle to fulfill its roles in both catabolism and anabolism ... 

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