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Non-Competitive Enzyme Inhibition

Sep 10, 2025

Overview

This lecture explains non-competitive enzyme inhibitors, their effects on enzyme activity and reaction rates, and their biological significance, especially in end product inhibition for cell regulation.

Non-Competitive Inhibitors: Mechanism and Effects

  • Non-competitive inhibitors bind to a site on the enzyme other than the active site (allosteric site).
  • Binding at this site disrupts hydrogen bonds and hydrophobic interactions, altering the enzyme's 3D structure.
  • This structural change prevents substrates from binding to the active site, stopping enzyme-substrate (ES) complex formation.
  • As a result, enzyme activity is reduced or completely halted.
  • The inhibition is reversible; when the inhibitor detaches, the enzyme regains its original shape and function.

Reaction Rate and Substrate Concentration

  • Increasing substrate concentration does not overcome non-competitive inhibition.
  • With non-competitive inhibitors, the maximum reaction rate (Vmax) decreases and cannot be restored by adding more substrate.
  • In contrast, with competitive inhibitors, Vmax can still be reached if enough substrate is added.

Biological Importance: End Product Inhibition

  • Non-competitive inhibition occurs naturally to regulate metabolic pathways and prevent excess product buildup.
  • In a sequence of enzyme-catalyzed reactions, the end product can non-competitively inhibit an earlier enzyme in the pathway.
  • This feedback mechanism is called end product inhibition, balancing production and preventing substrate depletion.
  • Example: Threonine is converted to isoleucine in the liver; excess isoleucine inhibits the enzyme that starts its synthesis to maintain both amino acids.

Key Terms & Definitions

  • Non-competitive inhibitor — a molecule that binds to an enzyme at a site other than the active site, reducing enzyme activity.
  • Allosteric site — a region on an enzyme other than the active site where molecules like inhibitors can bind.
  • Vmax — the maximum rate of an enzymatic reaction when the enzyme is saturated with substrate.
  • End product inhibition — regulation where the final product of a pathway inhibits an enzyme involved earlier in its synthesis.

Action Items / Next Steps

  • Review diagrams comparing competitive and non-competitive inhibition.
  • Remember that increasing substrate concentration does not affect non-competitive inhibition.
  • Study examples of end product inhibition for exam preparation.