Enzyme Kinetics: Reversible Inhibition

Enzyme Kinetics: Reversible Inhibition

Overview of Enzyme Inhibition

Enzyme inhibition refers to the process by which the activity of an enzyme is decreased or stopped due to the interaction with a specific molecule known as an inhibitor. Reversible inhibition is a key regulatory mechanism in biochemistry, affecting metabolic pathways and drug action.

• Enzyme: A biological catalyst that speeds up chemical reactions in living organisms.

• Inhibitor: A molecule that binds to an enzyme and decreases its activity.

• Reversible inhibition: The inhibitor can bind and dissociate from the enzyme, allowing for regulation of enzyme activity.

Types of Reversible Inhibition

• Competitive Inhibition: The inhibitor resembles the substrate and binds to the active site, preventing substrate binding.

• Noncompetitive Inhibition: The inhibitor binds to a site other than the active site, altering enzyme function without blocking substrate binding.

• Uncompetitive Inhibition: The inhibitor binds only to the enzyme-substrate complex, preventing the reaction from completing.

• Mixed Inhibition: The inhibitor can bind to either the enzyme or the enzyme-substrate complex, affecting both substrate binding and catalysis.

Effects on Kinetic Parameters

The two main kinetic parameters affected by inhibitors are:

• Vmax: The maximum velocity of the enzyme-catalyzed reaction.

• Km: The substrate concentration at which the reaction rate is half of Vmax.

Type of Inhibition	Vmax	Km
Competitive	No change	Increased
Noncompetitive	Decreased	No change
Uncompetitive	Decreased	Decreased
Mixed	Decreased	Increased or Decreased

Lineweaver-Burk Plot Patterns

The Lineweaver-Burk plot (double reciprocal plot) is used to distinguish between types of inhibition by plotting $1/V$ versus $1/[S]$.

• Competitive inhibition: Lines intersect on the y-axis (Vmax unchanged, Km increased).

• Noncompetitive inhibition: Lines intersect on the x-axis (Km unchanged, Vmax decreased).

• Uncompetitive inhibition: Lines are parallel (both Vmax and Km decreased).

• Mixed inhibition: Lines intersect left of the y-axis (both Vmax and Km affected).

Key Equations

• Michaelis-Menten Equation:

$V = \frac{V_{max}[S]}{K_m + [S]}$

• Lineweaver-Burk Equation:

$\frac{1}{V} = \frac{K_m}{V_{max}} \cdot \frac{1}{[S]} + \frac{1}{V_{max}}$

Summary Table: Effects of Inhibitors

Inhibitor Type	Active Site Binding	Effect on Vmax	Effect on Km	Lineweaver-Burk Pattern
Competitive	Yes	No change	Increased	Intersect at y-axis
Noncompetitive	No	Decreased	No change	Intersect at x-axis
Uncompetitive	No (binds ES complex)	Decreased	Decreased	Parallel lines
Mixed	No	Decreased	Increased or Decreased	Intersect left of y-axis

Example

• Pharmacology: Many drugs act as enzyme inhibitors, such as statins (competitive inhibitors of HMG-CoA reductase) used to lower cholesterol.

Additional info: The handwritten diagrams at the bottom of the page likely represent the different Lineweaver-Burk plot patterns for each inhibition type, as described above.