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Suicide Inhibition

Mechanism-based inhibition (also called suicide inhibition) occurs when an enzyme binds to a competitive inhibitor and forms an irreversible complex with it

  • Covalent bonds are formed during the normal catalysis reaction, preventing the inhibitor from being released

  • The only way to restore enzyme activity is to synthesise new enzymes (inactivated enzymes are permanently inhibited)

An example of mechanism-based inhibitor is penicillin, which inhibits specific transpeptidases from synthesising the bacterial cell wall

  • This results in the destruction of the bacterial cell, as the bacteria can no longer regulate the the hydrostatic pressure within the cell and lyses (bursts)making penicillin a highly effective antibiotic (targets prokaryotic cells only)

Penicillin is a highly effective antibiotic as it targets a feature unique to prokaryotic cells (the peptidoglycan cell wall)

  • However, certain strains of bacteria are evolving modified versions of the transpeptidase that have low affinity for penicillin

  • These strains of bacteria are increasingly resistant to penicillin treatments and can potentially transfer this resistance via bacterial conjugation

Penicillin Action
penicillin%201
Penicillin-Induced Cell Lysis
Cell Lysis (Timecourse)