Amphibolic reactions, citric acid cycle

Apart from the production of NADH and FADH2, which are the high-energy fuels of electron transport, the citric acid cycle has two other major functions. Several of its intermediate compounds are used to synthesize other cell constituents. This, the provision of molecules for other metabolic or biosynthetic pathways, is the anabolic function of the cycle (Table 12.1). Alternatively, certain other processes occurring within the cell may produce intermediates of the citric acid cycle. These compounds enter the reactions of the cycle, and their degradation involves the catabolic role of the cycle. These two major capabilities classify the citric acid cycle as an amphibolic pathway (Greek amphi meaning both sides ). 

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. 

This reaction, which produces oxaloacetate from pyruvate, provides a connection between the amphibolic citric acid cycle and the anabolism of sugars by gluconeogenesis. On this same topic of carbohydrate anabolism, we should note again that pyruvate cannot be produced from acetyl-GoA in mammals. Because acetyl-GoA is the end product of catabolism of latty acids, we can see that mammals could not exist with fats or acetate as the sole carbon source. The intermediates of carbohydrate metabolism would soon be depleted. Garbohydrates are the principal energy and carbon source in animals (Figure 19.11), and glucose is especially critical in humans because it is the preferred fuel for our brain cells. Plants can carry out the conversion of acetyl-GoA to pyruvate and oxaloacetate, so they can exist without carbohydrates as a carbon source. The conversion of pyruvate to acetyl-GoA does take place in both plants and animals (see Section 19.3). 

We can also make some generalizations about amino acid metabolism in terms of the relationship of the carbon skeleton to the citric acid cycle and the related reactions of pyruvate and acetyl-GoA (Figure 23.7). The citric acid cycle is amphibolic it has a part in both catabohsm and anabolism. The anabolic aspect of the citric acid cycle is of interest in amino acid biosynthesis. The catabolic aspect is apparent in the breakdown of amino acids, leading to their eventual excretion, which takes place in reactions related to the citric acid cycle. 

---