KEY VALUES

• Vmax
  – Maximal rate of a reaction (every active site bound by substrate)
• Km
  – Inversely proportional to binding affinity of enzyme to substrate

ENZYME INHIBITION

• Occurs when a substance reduces activity of an enzyme

Types of inhibition

• Competitive
  – Substrate & inhibitor compete for active site
  – Greater [S] overcomes inhibition
  – Increases the apparent Km but does NOT affect Vmax
• Noncompetitive
  – Inhibitor reversibly binds to enzyme outside of active site to deactivate it.
  – Enzymes regain function when inhibitor removed from system
  – Does NOT change Km but lowers Vmax

NOT uncompetitive inhibition in which inhibitors bind enzyme-substrate complexes

• Uncompetitive inhibition: requires preassembled enzyme-substrate complexes–>more effective when [S] is high
• Irreversible
  – Inhibitor binds to and permanently deactivates enzyme
  – Only overcome by synthesis of new enzymes

CLINICAL CORRELATION

• Heavy metals (mercury & lead)
  – Irreversible inhibitors: bind tightly to sulfur groups in enzymes
  – Permanently deactivate them
• Ethylene glycol (antifreeze) metabolites
  – Toxic to human body
  – Ethanol (competitive inhibitor): used to inhibit alcohol dehydrogenase active site to prevent metabolism of ethylene glycol
• Angiotension-converting enzyme (ACE) inhibitors
  – Blood pressure lowering agents: noncompetitively inhibit ACE
  – Prevent formation of angiotensin (acts on kidneys to inc. blood pressure)