Inhibitors: MDCAT Biology notes
Inhibitors MDCAT notes: irreversible and reversible enzyme inhibition, competitive vs non-competitive inhibitors, malonate, penicillin and heavy metals.
What inhibitors are
An inhibitor is a substance that combines with an enzyme and reduces its activity. Many drugs, poisons and antibiotics work this way. The cell also uses inhibition to control its metabolism.
Irreversible and reversible inhibitors
| Irreversible | Reversible |
|---|---|
| Bind permanently, often with covalent bonds | Bind temporarily with weak linkages (non-covalent), and can be removed |
| Permanently inactivate or destroy the enzyme | Enzyme activity returns when the inhibitor leaves |
| Examples: heavy metal ions such as $\mathrm{Hg^{2+}}$, $\mathrm{Pb^{2+}}$ and $\mathrm{Ag^{+}}$; nerve gases | Two types: competitive and non-competitive |
Competitive inhibitors
- These are structural analogues of the substrate: their shape is so similar that they fit the active site.
- They compete with the substrate, not with the enzyme, for the active site. While an inhibitor occupies the site, the substrate cannot enter.
- They are reversible, and the inhibitor is not chemically changed by the enzyme.
- The inhibition can be overcome by adding more substrate, because the substrate then out-competes the inhibitor.
- Because more substrate is needed to reach half-maximum speed, the apparent $K_m$ increases. $V_{max}$ is unchanged.
Classic example:malonate (malonic acid) competitively inhibits succinic dehydrogenase, the Krebs cycle enzyme that normally acts on succinate. Adding plenty of succinate does reverse this inhibition. Penicillin is taught as an inhibitor of the bacterial enzyme that builds cell walls. Sulphonamides are another drug example of substrate-analogue inhibitors.
Non-competitive inhibitors
- These have a different structure from the substrate.
- They bind at a site other than the active site, called the allosteric site.
- Binding distorts the enzyme's shape, so the active site no longer fits the substrate properly.
- Adding substrate does not reverse the effect. The degree of inhibition depends only on inhibitor concentration.
- Example: cyanide inhibits cytochrome oxidase.
Comparison
| Feature | Competitive | Non-competitive |
|---|---|---|
| Binding site | Active site | Allosteric site |
| Shape vs substrate | Similar (analogue) | Different |
| Reversed by more substrate? | Yes | No |
| $K_m$ / $V_{max}$ | $K_m$ rises; $V_{max}$ unchanged | $V_{max}$ falls |
Worked example
Question: A poisoned patient recovers after a large dose of the enzyme's normal substrate is injected. What kind of inhibitor was the poison?
Answer: A competitive, reversible inhibitor. Only competitive inhibition is overcome by flooding the enzyme with substrate.
Common MDCAT traps
- Competitive inhibitors compete with the substrate, not the enzyme.
- They are analogous (similar in shape) to the substrate.
- Excess succinate does reverse malonate inhibition, so any statement saying it does not is incorrect.
- Non-competitive inhibitors act at the allosteric site and distort the enzyme's shape.
- A competitive inhibitor raises $K_m$. It does not lower it.
Quick revision
- Inhibitors reduce enzyme activity.
- Reversible inhibitors form weak bonds.
- Heavy metal ions inhibit enzymes.
- Malonate inhibits succinic dehydrogenase competitively.
- Competitive inhibition is neutralized by more substrate.