Amino acid nitrogen transamination

Transamination is the process by which an amino group, usually from glutamate, is transferred to an ot-keto acid, with formation of the corresponding amino acid plus oi-ketoglutarate. Thus, transamination provides a route for redistribution of amino acid nitrogen. Transamination reactions are catalyzed by transaminases (aminotransferases) (see here). 

Transamination channels a-amino acid nitrogen into glutamate. L-Glutamate dehydrogenase (GDH) occupies a central position in nitrogen metabolism. 

The alanine cycle accomplishes the same thing as the Cori cycle, except with an add-on feature (Fig. 17-11). Under conditions under which muscle is degrading protein (fasting, starvation, exhaustion), muscle must get rid of excess carbon waste (lactate and pyruvate) but also nitrogen waste from the metabolism of amino acids. Muscle (and other tissues) removes amino groups from amino acids by transamination with a 2-keto acid such as pyruvate (oxaloacetate is the other common 2-keto acid). 

The amino acids, aspartate and glutamate, are not taken up from the blood but are synthesised in the brain. This requires nitrogen (for the -NH2 groups) which is obtained from branched-chain amino acids via transamination, as in other tissues. 

Glutamate provides the amino group for the synthesis of many other amino acids through transamination reactions in all cells. These amino acids are then used for protein synthesis and other aspects of nitrogen metabolism. The majority of animals are dependent on plant or animal proteins for fixed nitrogen, for their nitrogen metabolism. 

The enzymes involved in the conversion of amino acid nitrogen into urea occur in the cytosol and in the mitosol and involve three different catalytic systems the Urea Cycle, The TCA cycle, and a transamination cycle, you might call them "Kreb s Tricycle."... 

A-11. Prokaryotes such as E. coli can make the carbon skeletons of all 20 amino acids and transaminate those carbon skeletons with nitrogen from glutamine or glutamate to complete the amino acid structures. 

The dominant reactions involved in removing amino acid nitrogen from the body are known as transaminations. This class of reactions funnels nitrogen from all free amino acids into a small number of compounds then, either they are oxidatively deaminated, producing ammonia, or their amine groups are converted to urea by the urea cycle. 

Fig. 38.9. Role of glutamate in urea production. Glutamate collects nitrogen from other amino acids by transamination reactions. This nitrogen can be released as NH4 by glutamate dehydrogenase (GDH). NH4" is also produced by other reactions (see Fig. 38.5). NH4+ provides one of the nitrogens for urea synthesis. The other nitrogen comes from aspartate and is obtained from glutamate by transamination of oxaloacetate.

Fig. 38.17. Conversion of alanine to glucose and urea. 1. Alanine, the key gluconeogenic amino acid, is transaminated to form pyruvate, which is converted to glucose. The nitrogen, now in glutamate, can be released as NH4 (2) or transferred to oxaloacetate to form aspartate (3). NH4 and aspartate enter the urea cycle, which produces urea. In summary, the carbons of alanine form glucose and the nitrogens form urea. Two molecules of alanine are required to produce one molecule of glucose and one molecule of urea.

There is a striking correlation between the form of nitrogen excretion and the pathway used by an animal to deaminate amino acids arising from proteolysis in ureoteles amino acids are transaminated with 2-oxo-glutarate to form glutamate, which in turn is attacked hy glutamate dehydrogenase, whereas in uricoteles amino acids are attack by amino acid oxidases. 

The reversibility of transamination has been exploited in the treatment of patients in renal failure. The traditional treatment was to provide them with a very low-protein diet, so as to minimize the total amount of urea that has to be excreted (section 9-3.1.4). However, they still have to be provided with the essential amino acids. If they are provided with the essential ketoacids, they can synthesize the corresponding essential amino acids by transamination, so reducing yet further their nitrogen burden. The only amino acid for which this is not possible is lysine - the ketoacid corresponding to lysine undergoes rapid non-enzymic condensation to pipecolic acid, which cannot be metabolized further. 

Most amino acids lose their nitrogen atom by a transamination reaction in which the -NH2 group of the amino acid changes places with the keto group of ct-ketoglutarate. The products are a new a-keto acid plus glutamate. The overall process occurs in two parts, is catalyzed by aminotransferase enzymes, and involves participation of the coenzyme pyridoxal phosphate (PLP), a derivative of pyridoxine (vitamin UJ. Different aminotransferases differ in their specificity for amino acids, but the mechanism remains the same. 

Pyridoxal phosphate mainly serves as coenzyme in the amino acid metabolism and is covalently bound to its enzyme via a Schiff base. In the enzymatic reaction, the amino group of the substrate and the aldehyde group of PLP form a Schiff base, too. The subsequent reactions can take place at the a-, (3-, or y-carbon of the respective substrate. Common types of reactions are decarboxylations (formation of biogenic amines), transaminations (transfer of the amino nitrogen of one amino acid to the keto analog of another amino acid), and eliminations. 

Macko, S.A., Estep, M.L.E., Engel, M.H. and Hare, RE. 1986 Kinetic fractionation of stable nitrogen isotopes during amino acid transamination. Geochimica et Cosmochimica Acta 50 2143-2146. 

Figure 11.3 is a flow model representing in extremely simple form the main relevant features of nitrogen metabolism. It is not difficult to propose a sufficient explanation why Bprot is isotopically heavier than the diet. We might expect that the net effect of transamination and deamination of amino acids is to remove isotopically lighter N (Macko et al. 1987). That is to say, we may expect that the equilibrium constant for the reaction ... 

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. 

Removal of a-amino nitrogen by transamination (see Figure 28-3) is the first catabolic reaction of amino acids except in the case of proline, hydroxyproline, threonine, and lysine. The residual hydrocarbon skeleton is then degraded to amphibolic intermediates as outhned in Figure 30-1. 

Transamination is the most common initial reaction of amino acid catabohsm. Subsequent reactions remove any additional nitrogen and restmcmre the hydrocarbon skeleton for conversion to oxaloacetate, a-ketoglutarate, pyruvate, and acetyl-CoA. 

The nitrogen contained in the amino acids is usually disposed of through the urea cycle. One of the early, if not the first, steps in amino acid catabolism involves a transamination using oxaloacetate or a-ketoglutarate as the amino-group acceptor. This converts the amino acid into a 2-keto acid, which can then be metabolized further. 

Figure 8.17 The metabolism of branched-chain amino acids in muscle and the fate of the nitrogen and oxoacids. The a-NH2 group is transferred to form glutamate which is then aminated to form glutamine. The ammonia required for aminab on arises from glutamate via glutamate dehydrogenase, but originally from the transamination of the branded chain amino acids. Hence, they provide both nitrogen atoms for glutamine formation.

Glutamate can then participate in the formation of other amino acids via the process called transamination. Transamination is the exchange of the amino group from an amino acid to a keto acid, and provides the most common process for the introduction of nitrogen into amino acids, and for the removal of nitrogen from them. The reaction is catalysed by a transaminase enzyme, and the coenzyme pyridoxal phosphate (PLP) is required. 

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