Regulation by covalent modification

Reversible covalent modifications

• Phosphorylation (Ser,Thr,Tyr,His) = Enzyme-P + ADP

• Adenylylation- (Tyr) = Enzyme-AMP + PPi (pyrophosphate)

• ADP-ribosylation, palmitoylation (lipid anchor)

• tertiary structure change

Phosphorylation

Kinases

Modify certain residues in target sequence, won’t dig through to find it-must be on surface ish

Some proteins will have multiple targets and kinases for finer control

What is an example of regulation by phosphorylation

Glycogen phosphorylase- can be activated by phosphorylation of a certain enzyme and deactivate by phosphorylation by another enzyme

process is reversible

Glycogen synthase

• Each phosphorylation site turns down activity

• Multiple sites act together to reduce activity- dimer switch

• Enzymes work both ways dont wanna make it then break it down immediately

isocitrate dehydorgenase

E-coil not mammals

off switch regulation

3 carboxyl groups with (-) charge, phosphorylation in active site- inactive

Irreversible covalent modification of primary structure

Zymogens (inactive enzymes) are activated by modification by other enzymes

eg. Digestive proteinases are modified by other proteinases (cleaving backbone)

Enzymes must then be destroyed or inactivated

Digestive enzyme regulatory path

• trypsinogen to trypsin by enteropeptidase

• tryspin makes more of itself

• Chymotrypsinogen to pi-Chymotrypsin by trypsin (catalytically active)

• Pi to a which is active (cleave after residue 15), pi and a create more a