Nitrogen excretion transamination

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 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 other amino acids can now be1 made from glutamic acid by transamination. At the end of their useful life they are transaminated back to glutamic acid which, in mammals at least, gives its nitrogen to urea for excretion. 

The nitrogen portion of amino acids is involved in transamination reactions in breakdown as well as in biosynthesis. Excess nitrogen is excreted in one of three forms ammonia (as ammonium ion), urea, and uric add (Figure 23.17). 

Amino acids are used by the body to form proteins, hormones, and enzymes. Transamination reactions can convert one amino acid into another to meet immediate needs. However, just as there are essential fatty acids, there are also essential amino acids. These amino acids cannot be synthesized in the body and must come from external sources. Humans require phenylalanine, valine, tryptophan, threonine, lysine, leucine, isoleucine, and methionine as essential amino acids. All other amino acids in the body can be synthesized at rates sufficient to meet body needs. If any one of the amino acids necessary to synthesize a particular protein is not available, then the other amino acids that would have gone into the protein are deaminated, and their excess nitrogen is excreted as urea (Ganong, 1963). 

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. 

The total amount of urea synthesized each day is several-fold higher than the amount that is excreted. Urea diffuses readily from the bloodstream into the large intestine, where it is hydrolysed by bacterial urease to carbon dioxide and ammonium. Much of the ammonium is reabsorbed and used in the liver for the synthesis of glutamate and glutamine, and then a variety of other nitrogenous compounds. Studies with urea show that a significant amount of label is found in essential amino acids. This may reflect intestinal bacterial synthesis of amino acids, or it may reflect the reversibility of the transamination of essential amino acids. 

The enzymes that catalyze transamination reactions are called aminotransferases. Each amino acid has its own aminotransferase. Transamination allows the amino groups of the various amino acids to be collected into a single amino acid (glutamate) so that excess nitrogen can be easily excreted. (Do not confuse transamination with transimination, discussed previously.)... 

Pyridoxal phosphate is regenerated from pyridoxamine phosphate in a reaction with a keto acid a-keto glutarate and oxaloacetate are very effective NHj acceptors (lower half of diagram). Evidently glutamate (or aspartate) is produced in the process, and the significance of transamination reactions rests primarily on the fact that nitrogen is passed on from here, i.e. from glutamate or aspartate to the final excretion product, urea (cf. Section 8). 

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