KEY VALUES
– Maximal rate of a reaction (every active site bound by substrate)
– Inversely proportional to binding affinity of enzyme to substrate
ENZYME INHIBITION
- Occurs when a substance reduces activity of an enzyme
Types of inhibition
– Substrate & inhibitor compete for active site
– Greater [S] overcomes inhibition
– Increases the apparent Km but does NOT affect Vmax
– 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)
