Glutamate nitrogen removal

This enzyme is found in many tissues, where it catalyzes the reversible oxidative deamination of the amino acid glutamate. It produces the citric acid cycle intermediate a-ketoglutarate, which serves as an entry point to the cycle for a group of glucogenic amino adds. Its role in urea synthesis and nitrogen removal is stiU controversial, but has heen induded in Figure 1-17-1 and Table 1-17-1. 

Figure 23.16 PATHWAY INTEGRATION The glucose—alanine cycle. During prolonged exercise and fasting, muscle uses branched-chain amino adds as fuel. The nitrogen removed is transferred (through glutamate) to alanine, which is released into the bloodstream. In the liver, alanine is taken up and converted into pyruvate for the subsequent synthesis of glucose.

Glutamate deamination is the main route of nitrogen removal in the body. Glutamate dehydrogenase is a mitochondrial enzyme in the Hver and the kidney. It can use NADH or NADPH as coen rmes for its catalytic activity. 

Figure 29-8. The glutaminase reaction proceeds essentially irreversibly in the direction of glutamate and NH/ formation. Note that the amide nitrogen, not the a-amino nitrogen, is removed.

The nitrogen from the pyrimidine bases is removed by transamination and dumped onto glutamate. The carbon skeleton ends up as C02. 

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. 

The key reaction, based on a method for removing glutamate residues in peptides, involves the conversion of the sole primary amine in the molecule to a diazo function. The most expeditious method consists of reacting (18-1) with nitrosyl chloride. The resulting diazo function in the product (18-2) can be displaced formally by oxygen from the enol form of the amide at the 7 position to form the iminolactone (18-3) the reaction may involve a spontaneous loss of nitrogen followed by capture of the resulting carbocation. Hydrolysis of the imine function in the product the leads to one of the key intermediates in this series, 7-ACA (18-4) [22]. 

All amino acids are derived from intermediates in glycolysis, the citric acid cycle, or the pentose phosphate pathway (Fig. 22-9). Nitrogen enters these pathways by way of glutamate and glutamine. Some pathways are simple, others are not. Ten of the amino acids are just one or several steps removed from the common metabolite from which they are derived. The biosynthetic pathways for others, such as the aromatic amino acids, are more complex. 

In peripheral tissues, two enzymes, namely glutamate dehydrogenase and glutamine synthetase, are important in the removal of reduced nitrogen, and particularly so in the brain, which is highly susceptible to free ammonia. 

Nitrogen may be removed from glutamate by glutamate dehydrogenase ... 

Glutamate plays a key role in removing nitrogen from amino acids. 

The first step in the catabolism of most amino acids is the transfer of the o-amino group from the amino acid to a-ketoglutarate (tx-KG). This process is catalyzed by transaminase (aminotransferase) enzymes that require pyridoxal phosphate as a cofactor. The products of this reaction are glutamate (Glu) and the a-ketoacid analog of the amino acid destined for catabolic breakdown. For example, aspartate is converted to its a-keto analog, oxalo-acetate, by the action of aspartate transaminase (AST), which also produces Glu from a-KG. The transamination process is freely reversible, and the direction in which the reaction proceeds is dependent on the concentrations of the reactants and products. These reactions do not effect a net removal of amino nitrogen the amino group is only transferred from one amino acid to another. 

For net removal of amino nitrogen, a second enzymatic reaction must take place that removes the amino group from Glu for disposal. The net removal of the amino nitrogen is accomplished by the mitochondrial enzyme glutamate dehydrogenase (GDH), which catalyzes the oxidative deamination of Glu to a-KG in a reaction that uses NAD+ as the electron acceptor. The enzyme can... 

Glutamate, glutamine, and aspartate also play central roles in removal of nitrogen from organic compounds. Transamination is reversible and is often the first step in catabolism of excess amino acids. 

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