Structural Biochemistry/Enzyme Regulation/Adneylation

Adenylation is a form of enzyme regulation on tyrosine to produce glutamine synthetase. The adenylylation reaction is catalyzed by adenylyl transferase enzyme on a molecule such as tyrosine.

During adenylation, the phosphodiester bond undergoes adenylation. A complex of adenylyl transferase and a regulatory protein causes an AMP unit to either attach to or be removed from the glutamine synthetase. The regulatory enzyme can exist in two forms, PA or PD. A complex of PA with adenylyl transerase catalyzes the attachment of the AMP unit to the glutamine synthetase, reducing its activity and forming an Adenylated glutamine synthetase. On the other hand, a PD and adenylyl transerase complex removes the AMP from glutamine synthetase, lowering its activity and creating a de-adenylated glutamine synthetase.

It is important to note that the regulatory enzyme can easily convert to its other form. PA can be converted to PD through the attachment of uridine monophosphate with help from uridylyl transferase while PD can convert to PA through hydrolysis. The rate of adenylation depends on the ratio of α-Ketoglutarate to Glutamine. α-Ketoglutarate stimulates uridylyl transferase to change PA to PD while at the same time inhibiting hydrolysis that changes PD to PA. The reverse is true for Glutamine. These catalytic activities are present only in the polypeptide chain, ensuring that the enzyme doesn't simultaneously catalyze uridylylation and hydrolysis.

Adenylation is an important form of regulation for amplifying signals such as for blood clotting and control of glycogen metabolism. Because Adenylation is an enzymatic cascade, it is easier for allosteric control as each enzyme can be a target for regulation. This is important for nitrogen metabolism in cells as it creates many regulatory sites, allowing a cell to fine tune its nitrogen production.

Reference
Berg, Jeremy Mark. Biochemistry/ Jeremy M. Berg, John L. Tymoczko, Lubert Stryer. -7th ed. P749-750.