3.4.1 Competitive Inhibition

Introduction

Enzyme inhibitors are molecules that decrease or stop enzyme activity. They are important in regulating metabolism, in drug action, and in understanding enzyme mechanisms. Competitive inhibition is one of the major types of enzyme inhibition, where the inhibitor competes with the substrate for binding to the active site.

Definition

Competitive Inhibition: A type of enzyme inhibition in which enzyme activity is blocked by the presence of a chemical that competes with the substrate for binding to the active site is called competitive inhibition.

In simple words: Competitive inhibition is when an inhibitor molecule competes with the substrate to bind to the active site of the enzyme.

Core Concept

• A competitive inhibitor is structurally similar to the normal substrate.
• It fits into the active site of the enzyme.
• However, it is not similar enough to substitute fully for the normal substrate in the chemical reaction.
• The enzyme cannot catalyze it to form reaction products.
• Competitive inhibition is usually temporary (reversible).
• The inhibitor eventually leaves the enzyme.
• It is also called reversible inhibition.
• The level of inhibition depends on the relative concentrations of substrate and inhibitor.
• If the concentration of the substrate is increased relative to the concentration of the inhibitor, the active site will usually be occupied by the substrate.

Detailed Explanation

Mechanism of Competitive Inhibition

• The competitive inhibitor has a shape similar to the substrate.
• It binds to the active site of the enzyme.
• This forms an enzyme-inhibitor (EI) complex.

• When the inhibitor is bound to the active site, the substrate cannot bind.
• The enzyme cannot catalyze the reaction.
• No product is formed.

• The inhibitor is not permanently bound.
• It can leave the active site.
• The enzyme can then bind to the substrate.
• This is why competitive inhibition is reversible.

• The substrate and inhibitor compete for the same active site.
• The one with the higher concentration or higher affinity will bind more often.
• If substrate concentration is increased, the substrate outcompetes the inhibitor.
• The rate of reaction increases.

Example of Competitive Inhibition

Malonate and Succinate Dehydrogenase:

• Succinate dehydrogenase catalyzes the formation of fumarate from succinate.
• Malonate is a competitive inhibitor of succinate dehydrogenase.
• Malonate is structurally similar to succinate.
• It binds to the active site of succinate dehydrogenase.
• But it cannot be converted to fumarate.
• Therefore, the enzyme is inhibited.

Equation: Succinate Succinate dehydrogenase→ Fumarate Malonate Succinate dehydrogenase→ No product

Structure:

Key Point: Malonate is similar to succinate but lacks one CH₂ group. It can bind to the active site but cannot be converted to product.

Importance of Competitive Inhibitors

• Competitive inhibitors are structurally similar to the substrate.
• They bind to the active site.
• This supports the Lock and Key model.

• Substances similar to the substrate are not acted upon by enzymes.
• This shows that enzymes are specific.

• Competitive inhibitors are used as drugs in the control of bacterial pathogens.
• Antibiotics known as sulphonamides are used to combat bacterial infection.

Sulphonamides as Competitive Inhibitors

• Sulphonamides are competitive inhibitors of the enzyme dihydropteroate synthase.
• This enzyme is involved in the synthesis of folic acid in bacteria.
• Folic acid is essential for bacterial growth and reproduction.
• Sulphonamides are structurally similar to PABA (para-aminobenzoic acid), the normal substrate.
• They bind to the active site of the enzyme.
• This blocks the synthesis of folic acid.
• Bacteria cannot grow and reproduce.
• This is why sulphonamides are effective antibiotics.

Effect of Substrate Concentration on Competitive Inhibition

Key Point: Competitive inhibition can be overcome by increasing the substrate concentration.

Comparison: Competitive vs Non-Competitive Inhibition

Effect of Competitive Inhibition on Enzyme Kinetics

Michaelis-Menten Equation: V₀ = V_max [S]K_m + [S]

• Vmax remains the same.
• Km increases.
• This means the enzyme has lower affinity for the substrate in the presence of the inhibitor.
• The inhibitor can be overcome by increasing substrate concentration.

Lineweaver-Burk Plot:

Intermediate Level

Mechanism in Detail

Importance of Competitive Inhibitors

Sulphonamides in Detail

Effect of Substrate Concentration

Effect on Enzyme Kinetics

Important Points

• 1. A type of enzyme inhibition in which enzyme activity is blocked by the presence of a chemical that compete with the substrate for binding to the active site is called competitive inhibition.
• 2. Usually, a competitive inhibitor is structurally similar to the normal substrate and so fits into the active site of the enzyme.
• 3. However, it is not similar enough to substitute fully for the normal substrate in the chemical reaction and the enzyme cannot catalyze it to form reaction products.
• 4. Competitive inhibition is usually temporary, and the inhibitor eventually leaves the enzyme hence it is also called reversible inhibition.
• 5. This means that the level of inhibition depends on the relative concentrations of substrate and inhibitor, since they are competing for places in enzyme active sites.
• 6. Therefore, if the concentration of the substrate is increased relative to the concentration of the inhibitor, the active site will usually be occupied by the substrate.
• 7. An example of inhibitor is malonate.
• 8. Succinate dehydrogenase that catalyzes the formation of fumarate from succinate is competitively inhibited by malonate.
• 9. The importance of competitive inhibitors is:
• - It supports lock and key hypothesis.
• - It shows that substances which are similar to substrate are not acted upon by enzymes.
• - Competitive inhibitors are used as drugs in the control of bacterial pathogens. Antibiotics known as sulphonamides are used to combat bacterial infection.

Remember

• - Competitive inhibitor = similar to substrate
• - Binds to active site
• - Blocks the substrate
• - Reversible = inhibitor can leave
• - Overcome by increasing substrate concentration
• - Example: Malonate inhibits succinate dehydrogenase
• - Drug use: Sulphonamides are competitive inhibitors
• - **Vmax** = unchanged
• - **Km** = increased
• - Lineweaver-Burk = intersect at y-axis
• - Supports Lock and Key hypothesis
• - Shows substrate specificity

Common Mistakes

• 1. Confusing competitive and non-competitive inhibition – Competitive = binds active site; Non-competitive = binds allosteric site.
• 2. Thinking competitive inhibition cannot be overcome – Competitive inhibition can be overcome by increasing substrate concentration.
• 3. Thinking Vmax decreases in competitive inhibition – Vmax remains unchanged; Km increases.
• 4. Thinking the inhibitor is identical to the substrate – The inhibitor is similar but not identical.
• 5. Forgetting that competitive inhibition is reversible – Competitive inhibition is usually reversible.
• 6. Confusing the examples – Malonate is a competitive inhibitor of succinate dehydrogenase.
• 7. Thinking competitive inhibitors are always drugs – Competitive inhibitors can be natural or synthetic; some are drugs.
• 8. Forgetting the importance of competitive inhibitors – They support the Lock and Key model and are used as drugs.
• 9. Thinking the inhibitor binds permanently – The inhibitor binds reversibly.
• 10. Confusing Km and Vmax – Km increases; Vmax remains unchanged.
• 11. Thinking substrate concentration has no effect – Substrate concentration affects the level of inhibition.
• 12. Forgetting the role of sulphonamides – Sulphonamides are competitive inhibitors used as antibiotics.

Quick Revision

• A type of enzyme inhibition in which enzyme activity is blocked by the presence of a chemical that compete with the substrate for binding to the active site is called competitive inhibition.
• Usually, a competitive inhibitor is structurally similar to the normal substrate and so fits into the active site of the enzyme.
• However, it is not similar enough to substitute fully for the normal substrate in the chemical reaction and the enzyme cannot catalyze it to form reaction products.
• Competitive inhibition is usually temporary, and the inhibitor eventually leaves the enzyme hence it is also called reversible inhibition.
• This means that the level of inhibition depends on the relative concentrations of substrate and inhibitor, since they are competing for places in enzyme active sites.
• Therefore, if the concentration of the substrate is increased relative to the concentration of the inhibitor, the active site will usually be occupied by the substrate.
• An example of inhibitor is malonate.
• Succinate dehydrogenase that catalyzes the formation of fumarate from succinate is competitively inhibited by malonate.
• The importance of competitive inhibitors is:
• It supports lock and key hypothesis.
• It shows that substances which are similar to substrate are not acted upon by enzymes.
• Competitive inhibitors are used as drugs in the control of bacterial pathogens. Antibiotics known as sulphonamides are used to combat bacterial infection.

60-Second Revision

• Competitive inhibitor = similar to substrate
• Binds to active site
• Blocks the substrate
• Reversible = inhibitor can leave
• Overcome by increasing substrate concentration
• Example: Malonate inhibits succinate dehydrogenase
• Drug use: Sulphonamides are competitive inhibitors
• **Vmax** = unchanged
• **Km** = increased
• Lineweaver-Burk = intersect at y-axis
• Supports Lock and Key hypothesis
• Shows substrate specificity
• Warning: Competitive inhibition can be overcome by increasing substrate concentration. Vmax remains unchanged; Km increases. The inhibitor is similar to the substrate but not identical. Competitive inhibition is reversible. Malonate inhibits succinate dehydrogenase. Sulphonamides are used as antibiotics.