Amphibolic cycle

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 not only a pathway for oxidation of two-carbon units—it is also a major pathway for interconversion of metabolites arising from transamination and deamination of amino acids. It also provides the substtates for amino acid synthesis by transamination, as well as for gluconeogenesis and fatty acid synthesis. Because it fimctions in both oxidative and synthetic processes, it is amphibolic (Figure 16—4). 

The citric acid cycle is amphibolic, since in addition to oxidation it is important in the provision of carbon skeletons for gluconeogenesis, fatty acid synthesis, and interconversion of amino acids. 

Humans can synthesize 12 of the 20 common amino acids from the amphiboHc intermediates of glycolysis and of the citric acid cycle (Table 28-1). While nutritionally nonessenrial, these 12 amino acids are not nonessential. AH 20 amino acids are biologically essential. Of the 12 nutritionally nonessential amino acids, nine are formed from amphibolic intermediates and three (cysteine, tyrosine and hydroxylysine) from nutritionally essential amino acids. Identification of the twelve amino acids that humans can synthesize rested primarily on data derived from feeding diets in which purified amino acids replaced protein. This chapter considers only the biosynthesis of the twelve amino acids that are synthesized in human tissues, not the other eight that are synthesized by plants. 

Figure 6.1 Scheme for catabolic and anabolic pathways (shown is their interrelation through ATP-ADP system and amphibolic metabolite cycle)... 

We should note at this point that the TCA cycle is more than just a means of producing NADH for oxidative phosphorylation. The pathway also provides a number of useful intermediates for other, often synthetic, pathways. For example, citrate is the starting substance for fat synthesis (Chapter 9) succinyl-CoA is required for haem production and 2-oxoglutarate and oxaloacetate in particular are involved with amino acid and pyrimidine metabolism. Pathways which have dual catabolic/anabolic functions are referred to as amphibolic . 

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 tricarboxylic acid cycle (see p. 136) is often described as the hub of intermediary metabolism. It has both catabolic and anabolic functions—it is amphibolic. 

During periods of hunger, muscle proteins serve as an energy reserve for the body. They are broken down into amino acids, which are transported to the liver. In the liver, the carbon skeletons of the amino acids are converted into intermediates in the tricarboxylic acid cycle or into acetoacetyl-CoA (see p. 175). These amphibolic metabolites are then available to the energy metabolism and for gluconeogenesis. After prolonged starvation, the brain switches to using ketone bodies in order to save muscle protein (see p. 356). 

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. 

The word amphibolic is often applied to those metabolic sequences that are part of a catabolic cycle and at the same time are involved in a biosynthetic (anabolic) pathway. Another term, anaplerotic, is sometimes used to describe pathways for the synthesis of regenerating substrates. This word, which was suggested by H. L. Komberg, comes from a Greek root meaning "filling up."80... 

The Amphibolic Nature of the TCA Cycle The Glyoxylate Cycle Permits Growth on a Two-Carbon Source... 

Amphibolic Pathways Explain, giving examples, what is meant by the statement that the citric acid cycle is amphibolic. 

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 ). 

Since the intermediates in the cycle are not formed or destroyed in its net operation, they may be considered to play catalytic roles. However, several intermediates are biosynthetic precursors of other metabolites (amphibolic role) and hence may become depleted. They are replenished (anaplerotic process) by other reactions to optimal concentrations. 

The Amphibolic Citric Acid Cycle Citric Acid Cycle Regulation... 

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