Enzyme Regulation: Inhibition Overview

Enzyme Regulation: Inhibition

• Inhibitors: Molecules that bind to an enzyme, preventing it from catalyzing reactions. They can block substrate access, slowing or stopping the reaction.
• Irreversible Inhibition: Occurs when the inhibitor forms covalent bonds with the enzyme, permanently disabling it.
• Reversible Inhibition: Occurs when the inhibitor's binding is weak and easily reversed. Common in metabolic regulation.
• Competitive Inhibition: The inhibitor binds to the same active site as the substrate. High inhibitor concentration stops the reaction completely as inhibitor and substrate compete.

Competitive Inhibition & Saturation Curves

• Competitive inhibitors alter the apparent Km (Michaelis constant) of the enzyme.
• By increasing the inhibitor concentration, the enzyme's affinity for substrate is reduced and the saturation curve shifts to the right, implying a greater substrate concentration is needed for the same reaction rate. Effectively higher Km.

Non-Competitive Inhibition & Saturation Curves

• Non-competitive inhibition: Inhibitors bind to a site other than the active site (allosteric site), changing the enzyme's shape and reducing its ability to bind the substrate.
• Non-competitive inhibitors alter the Vmax of the enzyme.
• Increasing the inhibitor concentration decreases the reaction rate (lower Vmax) regardless of substrate concentration.
  • The saturation curve stays similar in shape just shifts down because the the maximum rate of the reaction is lowered.

Overcoming Competitive Inhibition

• Increasing substrate concentration can outcompete the inhibitor for the active site, restoring enzyme activity.

Importance of Inhibitors

• Inhibitors play a crucial regulatory role in metabolism, regulating the rates of biochemical pathways.

Reversible vs Irreversible Inhibition

• Reversible inhibition involves weak binding, allowing the inhibitor to detach and enzyme function to return.
• Irreversible inhibition involves strong covalent bonding, permanently disabling the target enzyme.

Allosteric Control on Enzyme Activity

• Allosteric Enzymes: Enzymes that have an allosteric site in addition to the active site. This site can be between subunits.
• Allosteric Site: A specific site on the enzyme (not the active site) where molecules (effectors) can bind.
• Allosteric sites have two conformations (active and inactive) that are in dynamic equilibrium.
  • Binding to an allosteric site can stabilize either the active or inactive conformation.
• Effectors: Molecules (activators or inhibitors) that bind to allosteric sites, regulating enzyme activity.

Feedback Inhibition (Negative Feedback)

• Feedback Inhibition: End-product(s) in a metabolic pathway regulate the first step of the pathway via an allosteric effect.

• High product levels act as an inhibitor, slowing further reaction rates.

• Low product level inhibits reduces the inhibition, increasing the rate.

• Feedback inhibition is a form of regulation within pathways preventing unnecessary synthesis of materials, ensuring resources are efficiently used.

This quiz explores key concepts of enzyme inhibition including irreversible and reversible inhibition, competitive inhibition, and saturation curves. Understand how inhibitors work and their effects on the enzyme's substrate affinity as illustrated in saturation curves.