The enzyme glutamine synthetase is regulated covalently and allosterically. The covalent modification is an adenylylation catalyzed by the enzyme adenylyl transferase (AT). AT catalyzes the reaction in which a specific tyrosine residue in glutamine synthetase reacts with ATP to form an ester between the phenolic hydroxyl group and the phosphate of the resultant AMP. That tyrosine residue lies very close to a catalytic site. Adenylylation inactivates the adjacent catalytic site. A glutamine synthetase molecule with all 12 sites adenylylated is completely inactive, whereas partial adenylylation yields partial inactivation.

Figure 20.9 shows regulatory mechanisms of the E. coli glutamine synthetase. Both processes are catalyzed by the same enzyme - a complex of adenylyl transferase (AT) and a regulatory protein, PII. The form of PII determines whether the AT-PII complex catalyzes adenylylation or deadenylylation.If PII is uridylyated, the AT-PII complex catalyzes deadenylylation. Deuridylylation of PII causes the AT-PII complex to catalyze adenylylation. The enzyme uridylyl transferase catalyzes uridylylation of PII. Deuridylylation of PII is catalyzed by a different enzyme. Uridylyl transferase is allosterically regulated. ATP and -ketoglutarate activate it. Glutamine inhibits it.