Glutamine nitrogen removal

Figure 8.4 General summary of metabolism of amino adds. Amino adds in blood can be derived from the diet or hydrolysis of endogenous protein. The nitrogen in the amino acids can be used to synthesise other nitrogen-containing compounds (e.g. glutamine - see Table 8.4) or removed as urea (Chapter 10). The amino acids are also used to synthesise proteins or peptides. The carbon can be converted to CO2, glucose or triacylglycerol, but, in humans, very little is converted into fat, so triacylglycerol is omitted from the figure.

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. 

Figure 24-11 Integration of the urea cycle with mitochondrial metabolism. Green lines trace the flow of nitrogen into urea upon deamination of amino acids or upon removal of nitrogen from the side chain of glutamine.

Let us first consider the situation under conditions of nitrogen excess (see fig. 21.5). The first regulatory protein in the cascade is converted into a uridylyl-removing enzyme. This enzyme hydrolyzes UMP from a PII 3 UMP protein that acts in concert with adenylyltransferase to form adenylate glutamine synthase. The resulting adenylylated enzyme is inactive. 

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. 

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. 

Fig. 39.9. Syntliesis and degradation of glutamine. Different enzymes catalyze the addition and the removal of the amide nitrogen of glutamine.

A compound formed by the combination of ammonium with glutamate. Most glutamine is metabolized by the liver to form glutamate and the ammonium nitrogen is converted to urea. In severe liver disease, ammonia is not removed and this leads to increased glutamine synthesis by the brain. Thus increased blood glutamine levels are often found in liver disease. 

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