As unnecessary activity within a cell can be wasteful or harmful, enzymes are regulated by four primary means: proteolytic cleavage (irreversible covalent modification), reversible covalent modification, control proteins, and allosteric interactions.

Enzymes select which reactions take place within a cell and, therefore, must regulate them. Catalytic activity is desirable only when needed, so enzymes are regulated by four primary means: proteolytic cleavage (irreversible covalent modification), reversible covalent modification, control proteins, and allosteric interactions.

Proteolytic cleavage (irreversible covalent modification): Many enzymes are released into their environment in an active form called a zymogen (or proenzyme). When specific peptide bonds on zymogens are cleaved, the zymogens become irreversibly activated. Activation of zymogens may be instigated by other enzymes, or by a change in the environment.

Reversible covalent modification: Some enzymes are activated or deactivated by phosphorylation or the addition of some other modifier (e.g. AMP). The removal of all modifiers is almost always done by hydrolysis.

Control proteins: Control proteins are protein subunits that associate with certain enzymes to activate or inhibit their activity (e.g. calmodulin, G-proteins).

Allosteric interactions: Allosteric regulation is the modification of an enzyme’s configuration through the binding of an activator or inhibitor at a specific binding site of the enzyme called the allosteric site. In allosteric inhibition, inhibitor molecules bind to an enzyme at the allosteric site. Their binding induces a conformational change that reduces the affinity of the enzyme’s active site for its substrate. The binding of this allosteric inhibitor changes the conformation of the enzyme and its active site, so the substrate is not able to bind. This prevents the enzyme from lowering the activation energy of the reaction, and the reaction rate is reduced. Allosteric activators can increase reaction rates. They bind to an allosteric site which induces a conformational change that increases the affinity of the enzyme’s active site for its substrate. This increases the reaction rate.

 

Practice Questions

 

Khan Academy

 

MCAT Official Prep (AAMC)

Biology Question Pack, Vol 2. Passage 15 Question 98

 

Key Points

• Enzymes select which reactions take place within a cell and, therefore, must regulate them. Catalytic activity is desirable only when needed, so enzymes are regulated by four primary means: proteolytic cleavage (irreversible covalent modification), reversible covalent modification, control proteins, and allosteric interactions.

• Proteolytic cleavage (irreversible covalent modification) is when specific peptide bonds on zymogens are cleaved; the zymogens become irreversibly activated.

• Reversible covalent modification is when some enzymes are activated or deactivated by phosphorylation or the addition of some other modifier.

• Control proteins are protein subunits that associate with certain enzymes to activate or inhibit their activity.

• Allosteric regulation is the modification of an enzyme’s configuration through the binding of an activator or inhibitor at a specific binding site of the enzyme.

Key Terms

zymogen: enzymes released into their environment in an active form.

phosphorylation: a biochemical process that involves the addition of phosphate to an organic compound.

catalytic activity: defined as the rate constant for the slow step

hydrolysis: the chemical breakdown of a compound due to reaction with water

allosteric site: a site other than the active site on an enzyme