Topic 6 - Enzyme Regulation & Feedback Inhibition

Question 1

Control of Enzyme Levels

Answer 1

1. Induction & repression of enzyme synthesis
2. Degradation of enzyme molecules

Question 2

Control of Substrate Availability

Answer 2

Ingestion, synthesis, degradation, and compartmentation of substrates.

Remember: Km of an enzyme exhibiting Michaelis-Menten kinetics lies within the steepest part of the curve. So velocity will be strongly affected by small changes in [S] if the Km lies within/above the normal concentration range of that substrate in the cell – “regulation by substrate availability.”

On the other hand, if Km lies far below the normal range of the substrate, then the velocity will not be significantly affected by changes in the substrate concentration – this enzyme is not regulated by substrate availability.

Question 3

Control of Enzyme Activity

Answer 3

1. Covalent Modification:
   a. Irreversible **Covalent Modification: Zymogen activation - Trypsin cleaves chymotrypsinogen
   b. Reversible **Covalent Modification: de/phosphorylation of the enzyme. May involve regulatory cascade (such as for PFK in glucose metabolism)
2. Non-Covalent Modification (reversible):
   a. Positive effectors: cause an enzyme to become active or more active
   b. Negative effectors = inhibitors:
3. Substrate cannot bind due to inhibitor already being bound
4. Substrate cannot bind due to change in substrate-binding site caused by inhibitor binding elsewhere on the enzyme
5. Substrate binds, but inactive due to conformational change induced by binding of inhibitor
6. Inhibitor cannot bind to free Enzyme. Substrate binds, but inhibitor can now bind due to change in regulatory site

Question 4

Simple Feedback Inhibition

Answer 4

A type of inhibition in which the end product of a multienzyme sequence inhibits the activity of an enzyme at or near the beginning of the pathway.

Question 5

Cumulative Feedback Inhibition

Answer 5

Each end product inhibits the first individual committed step. Also, each end product partially inhibits the first common committed step.

If there are two products, both end products can fully inhibit the first common committed step.

Question 6

Concerted Feedback Inhibition

Answer 6

Each end product inhibits the first individual committed step. Together, they inhibit the first common committed step. Alone, neither has an effect on the first step (no partial inhibition like in cumulative feedback inhibition).