Learning Objective 

Differentiate among Michaelis–Menten kinetics, competitive inhibition, and noncompetitive inhibition, and apply this knowledge to drug mechanisms that affect enzyme activity, potency, and efficacy.

Enzyme kinetics describes how enzymes interact with substrates and how this affects the rate of biochemical reactions. Understanding enzyme kinetics is crucial for pharmacology, biochemistry, and solving medical problems.

Michaelis–Menten Kinetics

• Km (Michaelis constant):
  • Substrate concentration at which velocity = ½ Vmax
  • Inverse relationship to affinity (↓Km = ↑affinity)
• Vmax:
  • Maximum reaction velocity
  • Directly proportional to enzyme concentration
• Curve Types:
  • Hyperbolic curve → Most enzyme kinetics (Michaelis–Menten)
  • Sigmoidal curve → Indicates positive cooperativity (e.g., aspartate transcarbamoylase, hemoglobin O₂ binding is a classic example outside this context)

Effects of Inhibitors on Michaelis–Menten Kinetics

Competitive Inhibition (Reversible)

• Mechanism: Inhibitor resembles substrate, binds active site
• Effect:
  • ↑ Km (↓ affinity)
  • Vmax unchanged (can be overcome by ↑[S])

Noncompetitive Inhibition

• Mechanism: Inhibitor binds allosteric site, not the active site
• Effect:
  • Vmax ↓ (enzyme activity reduced)
  • Km unchanged (affinity unaffected)

Lineweaver–Burk Plot

The double reciprocal plot (1/V vs 1/[S]) helps distinguish inhibitors.

• X-axis (1/[S]): Closer to zero → lower Km (higher affinity)
• Y-axis (1/V): Closer to zero → higher Vmax
• Competitive inhibitors: Lines cross at the Y-axis (same Vmax, different Km).
• Noncompetitive inhibitors: Lines cross at the X-axis (same Km, different Vmax).

Summary Table of Inhibition

Visual Mnemonics

• Km = “Affinity Constant” → Inversely related to affinity
• Vmax = “Maximum Capacity” → How many enzymes are available
• Competitive = Competes at the active site, raises Km
• Noncompetitive = No competition, shuts down enzymes, lowers Vmax

Activity: