Glutamine synthase, function

Formation of glutamine is catalyzed by mitochondrial glutamine synthase (Figure 29-7). Since amide bond synthesis is coupled to the hydrolysis of ATP to ADP and P , the reaction strongly favors glutamine synthesis. One function of glutamine is to sequester ammonia in a nontoxic form. 

The urea cycle is a unique function of the liver. Excess ammonia formed in other tissues must be carried in a nontoxic form to the liver. In many tissues glutamine serves as the carrier of excess nitrogen. The glutamine is formed in the tissues in a reaction, catalyzed by glutamine synthase, that combines NH3 with glutamate. 

The glutamine synthase regulatory system has another important function. Protein Pll stimulates the dephosphorylation of the enhancer-binding transcriptional regulator NRI-P (NtrC-P). This slows transcription of the glutamine S5mthase gene (see Fig. 

For the biosynthetic transfer of ammonia, the carboxylic acid function of glutamic acid is activated by ATP. In case phosphinothricin is present, this undergoes the same activation. The resulting phosphorylated phosphinothricin inhibits glutamine synthase in a competitive manner and functions as a substrate analogue- and transition state analogue-inhihitor. [13]... 

Condensation of CO2, ammonia, and ATP to form carbamoyl phosphate is catalyzed by mitochondrial carbamoyl phosphate synthase I (reaction 1, Figure 29-9). A cytosolic form of this enzyme, carbamoyl phosphate synthase II, uses glutamine rather than ammonia as the nitrogen donor and functions in pyrimidine biosynthesis (see Chapter 34). Carbamoyl phosphate synthase I, the rate-hmiting enzyme of the urea cycle, is active only in the presence of its allosteric activator JV-acetylglutamate, which enhances the affinity of the synthase for ATP. Formation of carbamoyl phosphate requires 2 mol of ATP, one of which serves as a phosphate donor. Conversion of the second ATP to AMP and pyrophosphate, coupled to the hydrolysis of pyrophosphate to orthophosphate, provides the driving... 

---