Enzymes speed up biological reactions by lowering activation energy, but cells must control when and how fast those reactions happen. Enzyme inhibition is one major way to slow or stop an enzyme. Inhibitors can be normal cell regulators, medicines, or dangerous poisons.
Understanding inhibition helps explain metabolism, drug action, and many diseases.
An inhibitor may block the active site, bind somewhere else on the enzyme, or shift the enzyme into a less active shape. Competitive inhibitors compete with substrate for the active site, while noncompetitive inhibitors reduce enzyme function even when substrate is present. Allosteric regulation occurs when a molecule binds at a regulatory site and changes enzyme activity, sometimes decreasing it and sometimes increasing it.
Many drugs work by inhibiting specific enzymes, while poisons often inhibit enzymes needed for nerve, blood, or energy function.
Key Facts
- Enzyme reaction: E + S ⇌ ES → E + P, where E is enzyme, S is substrate, and P is product.
- Competitive inhibition increases apparent Km but does not change Vmax if enough substrate is added.
- Noncompetitive inhibition decreases Vmax because some enzyme molecules are made less active, even at high substrate concentration.
- Km is the substrate concentration at which reaction rate is 1/2 Vmax.
- Higher inhibitor concentration usually lowers reaction rate by reducing active enzyme activity or substrate binding.
- Many medicines are enzyme inhibitors, such as statins inhibiting HMG-CoA reductase and aspirin inhibiting cyclooxygenase.
Vocabulary
- Enzyme
- A biological catalyst, usually a protein, that speeds up a chemical reaction without being used up.
- Active site
- The specific region of an enzyme where the substrate binds and the reaction takes place.
- Competitive inhibitor
- A molecule that resembles the substrate and competes for binding at the enzyme active site.
- Noncompetitive inhibitor
- A molecule that binds away from the active site and reduces enzyme activity by changing the enzyme's shape or function.
- Allosteric site
- A regulatory binding site on an enzyme that is separate from the active site and can change enzyme activity.
Common Mistakes to Avoid
- Saying all inhibitors bind at the active site is wrong because noncompetitive and allosteric inhibitors bind at other sites and change enzyme activity indirectly.
- Assuming adding more substrate always fixes inhibition is wrong because extra substrate can overcome many competitive inhibitors but not true noncompetitive inhibitors.
- Confusing Km with Vmax is wrong because Km describes the substrate level needed for half-maximal rate, while Vmax is the highest reaction rate under given conditions.
- Treating all allosteric regulation as inhibition is wrong because allosteric molecules can either decrease or increase enzyme activity depending on how they change enzyme shape.
Practice Questions
- 1 An enzyme has Vmax = 120 micromoles per minute without inhibitor. A noncompetitive inhibitor reduces active enzyme function by 40 percent. What is the new Vmax?
- 2 A reaction has Km = 5 mM without inhibitor. With a competitive inhibitor, the apparent Km becomes 20 mM while Vmax stays 80 micromoles per minute. By what factor did the apparent Km increase?
- 3 A student observes that adding a large amount of substrate restores the reaction rate close to normal. Which type of inhibition is most likely, competitive or noncompetitive, and what evidence supports the choice?