explain the effects of reversible inhibitors, both competitive and non-competitive, on enzyme activity

Published by Patrick Mutisya · 14 days ago

Cambridge A-Level Biology – Factors that affect enzyme action

Factors that affect enzyme action – Reversible Inhibitors

Learning Objective

Explain how reversible inhibitors, both competitive and non‑competitive, influence enzyme activity.

Key Concepts

  • Enzymes are biological catalysts that lower the activation energy of reactions.

  • Enzyme activity can be altered by substances that bind to the enzyme without permanently damaging it – these are reversible inhibitors.

  • Two main types of reversible inhibition:

    • Competitive inhibition

    • Non‑competitive inhibition

Competitive Inhibition

In competitive inhibition the inhibitor resembles the substrate and competes for the active site.

Key features:

  • The inhibitor binds only to the free enzyme (E), not to the enzyme–substrate complex (ES).

  • Increasing substrate concentration can overcome inhibition.

  • Maximum reaction velocity (\$V{\max}\$) remains unchanged, but the apparent Michaelis constant (\$Km\$) increases.

Modified Michaelis–Menten equation:

\$v = \frac{V{\max}[S]}{Km\left(1+\frac{[I]}{K_i}\right)+[S]}\$

where \$[I]\$ is inhibitor concentration and \$K_i\$ is the inhibition constant.

Non‑competitive Inhibition

In non‑competitive inhibition the inhibitor binds to an allosteric site, distinct from the active site.

Key features:

  • The inhibitor can bind to both free enzyme (E) and the enzyme–substrate complex (ES).

  • Increasing substrate concentration cannot overcome inhibition.

  • Maximum reaction velocity (\$V{\max}\$) decreases, while the apparent \$Km\$ remains unchanged.

Modified Michaelis–Menten equation:

\$v = \frac{V{\max}\left(1+\frac{[I]}{Ki}\right)^{-1}[S]}{K_m+[S]}\$

Comparison of Competitive and Non‑competitive Inhibition

FeatureCompetitive InhibitionNon‑competitive Inhibition
Binding siteActive site (substrate‑like)Allosteric site (different from active site)
Enzyme form boundOnly free enzyme (E)Both free enzyme (E) and enzyme‑substrate complex (ES)
Effect on \$V_{\max}\$UnchangedDecreases
Effect on \$K_m\$Increases (apparent \$K_m\$)Unchanged
Can be overcome byIncreasing substrate concentrationCannot be overcome by substrate
Typical exampleAnalogue of substrate (e.g., methotrexate inhibiting dihydrofolate reductase)Heavy metals binding to allosteric sites (e.g., lead inhibiting ALAD)

Illustrative Diagram

Suggested diagram: Graphical representation of Michaelis–Menten curves showing (a) competitive inhibition – same \$V{\max}\$, higher \$Km\$; (b) non‑competitive inhibition – lower \$V{\max}\$, unchanged \$Km\$.

Summary

  1. Reversible inhibitors bind non‑covalently and can dissociate from the enzyme.

  2. Competitive inhibitors compete with substrate for the active site; they raise \$Km\$ but do not affect \$V{\max}\$.

  3. Non‑competitive inhibitors bind elsewhere, reducing \$V{\max}\$ without altering \$Km\$.

  4. Understanding these effects helps predict how drugs and toxins influence metabolic pathways.

Key Points to Remember

  • Increase in \$K_m\$ means a lower affinity for substrate.

  • Decrease in \$V_{\max}\$ indicates fewer active enzyme molecules are available.

  • The type of inhibition determines whether increasing substrate concentration can restore enzyme activity.