Regulation of Enzyme Activity
High-Yield Summary
- Feedback (negative feedback) inhibition: downstream product regulates an earlier enzyme, slowing the pathway once enough product exists.
- Feed-forward regulation: an early intermediate activates a later enzyme, preparing the pathway ahead of demand.
- Four reversible inhibition types differ by binding site and effect on Km/Vmax: competitive, noncompetitive, uncompetitive, mixed.
- Irreversible inhibition permanently disables the enzyme, usually via a covalent bond at the active site — only new enzyme synthesis restores activity.
- Zymogens (proenzymes) are inactive until cleaved — e.g., trypsinogen → trypsin (by enteropeptidase), which then activates chymotrypsinogen and pepsinogen.
Key Terms
- Feedback inhibition
- A pathway's downstream product inhibits an enzyme earlier in the same pathway.
- Allosteric site
- A regulatory binding site distinct from the active site.
- Zymogen (proenzyme)
- Inactive enzyme precursor activated later, usually by proteolytic cleavage.
- Covalent modification
- Addition of a chemical group that changes enzyme shape, activity, or stability.
Feedback vs. Feed-Forward Regulation
| Feedback (Negative) | Feed-Forward |
|---|---|
| Downstream product regulates an earlier enzyme | Earlier intermediate activates a later enzyme |
| Reacts to product already made | Anticipates product still to come |
Reversible Inhibition: Km/Vmax Effects
| Type | Binding Site → Km / Vmax / Lineweaver-Burk |
|---|---|
| Competitive | Active site → Km ↑, Vmax unchanged, intersects on y-axis |
| Noncompetitive | Allosteric site → Km unchanged, Vmax ↓, intersects on x-axis |
| Uncompetitive | ES complex only → Km ↓, Vmax ↓, parallel lines |
| Mixed | Allosteric site (free E or ES) → Vmax always ↓, Km ↑ or ↓ by preference |
Zymogen Activation Cascade (Digestive Proteases)
- 1Trypsinogen (inactive) is cleaved by enteropeptidase in the duodenum → active trypsin.
- 2Trypsin cleaves chymotrypsinogen → active chymotrypsin.
- 3Pepsinogen is activated separately, by the stomach's low pH → active pepsin.
Common MCAT Trap
- Competitive inhibition is overcome by adding more substrate (Vmax unchanged); noncompetitive is NOT (Vmax drops regardless of [S]) — a frequently tested distinction.
- Uncompetitive inhibitors bind ONLY the enzyme-substrate complex, never free enzyme — this is what makes both Km and Vmax drop together (parallel Lineweaver-Burk lines).
- Zymogens store dangerous enzymes safely — activation by cleavage, not by synthesis of new active enzyme from scratch.
Quick Recall
Which inhibition type leaves Vmax unchanged but increases Km?
Which inhibition type decreases both Km and Vmax with parallel Lineweaver-Burk lines?
What activates trypsinogen, and what does active trypsin do next?
What distinguishes irreversible from reversible inhibition mechanistically?