Transamination citric acid cycle

The amino acids are required for protein synthesis. Some must be supplied in the diet (the essential amino acids) since they cannot be synthesized in the body. The remainder are nonessential amino acids that are supplied in the diet but can be formed from metabolic intermediates by transamination, using the amino nitrogen from other amino acids. After deamination, amino nitrogen is excreted as urea, and the carbon skeletons that remain after transamination (1) are oxidized to CO2 via the citric acid cycle, (2) form glucose (gluconeogenesis), or (3) form ketone bodies. 

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 Takes Part in Gluconeogenesis, Transamination,... 

Figure 16-4. Involvement of the citric acid cycle in transamination and gluconeo-genesis. The bold arrows indicate the main pathway of gluconeogenesis.

The carbon skeletons of asparagine and aspartate ultimately enter the citric acid cycle as oxaloacetate. The enzyme asparaginase catalyzes the hydrolysis of asparagine to aspartate, which undergoes transamination with a-lcetoglutarate to yield glutamate and oxaloacetate (Fig. 18-29). 

The two transamination steps in the pathways may be linked, as indicated in Fig. 17-5, to form a complete cycle that parallels the citric acid cycle but in which 2-oxoglutarate is oxidized to succinate via glutamate and y-aminobutyrate. No thiamin diphosphate is required, but 2-oxoglutarate is reductively aminated to glutamate. The cycle is sometimes called the y-aminobutyrate shunt, and it plays a significant role in the overall oxidative processes of brain tissue. 

The fumarate produced in the urea cycle can enter directly into the citric acid cycle and be converted into oxaloacetate. Oxaloacetate can then be either transaminated to aspartate which feeds back into the urea cycle, or be converted into citrate, pyruvate or glucose. 

Fig. 2. The urea cycle and the citric acid cycle are linked by lumarate and the transamination of oxaloacetate to aspartate.

The amino acid aspartate can be metabolized as what citric acid cycle intermediate after transamination ... 

Some Aa are transaminated or deaminated to ketoacids, which are then metabolised by many pathways, including the Krebs-citric acid cycle (Figure 2.3). Others are metabolised to ammonia and urea by the Krebs-Fienseleit urea cycle (Figure 2.4). 

Pyrophosphate is rapidly hydrolyzed, and so the equivalent of four molecules of ATP are consumed in these reactions to synthesize one molecule of urea. The synthesis of fumarate by the urea cycle is important because it links the urea cycle and the citric acid cycle (Figure 23.17). Fumarate is hydrated to malate, which is in turn oxidized to oxaloacetate. Oxaloacetate has several possible fates (1) transamination to aspartate, (2) conversion into glucose by the gluconeogenic pathway, (3) condensation with acetyl CoA to form citrate, or (4) conversion into pyruvate. 

Figure 23.17. Metabolic lutegratiou of Nitrogeu Metabolism. The urea cycle, the citric acid cycle, and the transamination of oxaloacetate are linked hy fumarate and aspartate.

Aspartate and asparagine are converted into oxaloacetate, a citric acid cycle intermediate. Aspartate, a four-carbon amino acid, is directly transaminated to oxaloacetate. 

The degradation of the hranched-chain amino acids employs reactions that we have encountered previously in the citric acid cycle and fatty acid oxidation. Leucine is transaminated to the corresponding a-ketoacid, a-ketoisocaproate. This a-ketoacid is oxidatively decarboxylated to isovaleryl CoA by the branched-chain a-ketoacid dehydrogenase complex. 

Succinate —> malate oxaloacetate by the citric acid cycle. Oxaloacetate —> aspartate by transamination, followed by pyrimidine synthesis. Carbons 4, 5, and 6. 

With regard to amino acid metabolism, the data are scarce but it is probable that these metabolites give rise to, or are derived from, the oxoacids of the citric acid cycle via transamination or analogous reactions. See the literature [60-62] for examples of such enzymes in the halophilic, thermophilic and methanogenic archaebacteria. 

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