Nitrogen metabolism transamination reactions

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 ... 

In contrast to transamination reactions that transfer amino groups, oxidative deamination by gutamate dehydrogenase results in the lib eration of the amino group as free ammonia (Figure 19.11). These reactions occur primarily in the liver and kidney. They provide a-ketoacids that can enter the central pathway of energy metabolism, and ammonia, which is a source of nitrogen in urea synthesis. 

The phosphate ester of the aldehyde form of vitamin B6, pyridoxal phosphate (pyridoxal-P or PLP), is required by many enzymes catalyzing reactions of amino acids and amines. The reactions are numerous, and pyridoxal phosphate is surely one of nature s most versatile catalysts. The story begins with biochemical transamination, a process of central importance in nitrogen metabolism. In 1937, Alexander Braunstein and Maria Kritzmann, in Moscow, described the transamination reaction by which amino groups can be transferred from one carbon skeleton to another.139 140 For example, the amino group of glutamate can be transferred to the carbon skeleton of oxaloacetate to form aspartate and 2-oxoglutarate (Eq. 14-24). 

This transamination reaction is a widespread process of importance in many aspects of the nitrogen metabolism of organisms. A large series of transaminases (aminotransferases), for which glutamate is most often one of the reactants, have been shown to catalyze the reactions of other oxoacids and amino acids.141-143... 

In the preceding sections, attention was focused on amino acid metabolism in the intact animal. We now examine the metabolic pathways of individual amino acids, which take place in the cells of various human tissues. The first reaction in the metabolic pathways of many amino acids is the loss of nitrogen through transamination or deamination. Conversely, the biosynthesis of many non-essential amino acids involves the addition of nitrogen to amino acid precursors amination and transamination. Decarboxylation, or loss of C02, is another reaction shared by many amino acids. 

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. 

Two types of reactions play prominent roles in amino acid metabolism. In transamination reactions, new amino acids are produced when a-amino groups are transferred from donor a-amino acids to acceptor a-keto acids. Because transamination reactions are reversible, they play an important role in both amino acid synthesis and degradation. Ammonium ions or the amide nitrogen of glutamine can also be directly incorporated into amino acids and eventually other metabolites. 

Alanine is an allosteric inhibitor of glutamine synthetase, an enzyme with a central role in nitrogen metabolism in the cell. Alanine participates in transamination reactions and in the glucose-alanine cycle. 

In addition to transamination reactions, one-carbon transfer reactions occur frequently in amino acid biosynthesis. A good example of a one-carbon transfer can be found in the reactions that produce the amino acids of the serine family. This family also includes glycine and cysteine. Serine and glycine themselves are frequently precursors in other biosynthetic pathways. A discussion of the synthesis of cysteine will give us some insight into the metabolism of sulfur, as well as that of nitrogen. 

Thus, we see that transaminases perform two vital functions in amino add metabolism. By taking part in the biosynthesis of nonessential amino acids, they provide a means to help readjust the relative proportions of amino acids to meet the particular needs of the body. This is a vital function because most of our diets do not contain amino acids in the exact proportions the body requires. Also, as we noted in Section 14.9, transamination reactions allow the nitrogen atoms of all amino acids to be transferred to a-keto acids to form glutamate and aspartate when disposal of nitrogen is necessary. 

The biological importance of this enzyme has already been discussed (section II). Its role in producing glutamate, as the first organic amino compound, in bacteria and plants seems reasonably well established. In animals, which do not have the ability to produce all amino compounds from a simple nitrogen source, the enzyme seems to be concerned with the removal of excess amino compounds (equations 2-5) as well as with the production of glutamate for conversion to the acid amide (section V.B) or to take part in transamination reactions to form the non-essential amino compounds. Cellular control of the direction in which reaction occurs may well lie in the ratio of the concentrations of the oxidised and reduced forms of the cofactor. This ratio is not a fixed quantity but depends on the metabolic activity of the cell (NAD and NADP are cofactors for many oxidation-reduction reactions) as well as on the availability of molecular oxygen for the terminal step in respiration, by which the reduced cofactor is reoxidised by the cytochrome system (section IV.A.1). 

Subsequent transamination reactions then provide the other amino acids needed for protein synthesis. Glutamine serves as a -NH2 donor in a number of biosynthetic reactions and Figure 35.4 shows how carbohydrate and nitrogen metabolism may be interrelated in the plaque. An additional source of amino acids within the interior may be provided by hydrolysis of matrix proteins. 

The transamination reaction is important biologically in amino acid metabolism. Simple aldehydes are rare in biological systems and are mostly masked as imines. Biochemists often refer to them as Schiff bases, which are a special class of aldehyde imine where the nitrogen atom is substituted by an alkyl or aryl group. The transamination reaction interconverts amino and carbonyl functionalities (Figure 14.32). The enzymes involved in the process are called transaminases, and they require pyridoxal phosphate as a cofactor. 

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. 

---