Enzyme Inhibition


Irreversible inhibition is a type of enzyme inhibition that permanently inactivates the enzyme by forming a strong covalent bond with an amino acid residue at or near the active site. This prevents the enzyme from catalyzing its normal reaction and reduces the overall enzyme activity in the system.

Irreversible inhibitors are often highly reactive compounds that target specific amino acid residues that are essential for the enzyme function. For example, some irreversible inhibitors react with serine or cysteine residues that have nucleophilic hydroxyl or sulfhydryl groups, respectively. These groups can attack the electrophilic center of the inhibitor and form a stable covalent bond.

Irreversible inhibition can be used as a tool to study the structure and function of enzymes, as well as to design drugs that selectively block the activity of certain enzymes involved in diseases. Some examples of irreversible inhibitors are:

  • Diisopropyl fluorophosphate (DIPF), a nerve agent that inhibits acetylcholinesterase, an enzyme that breaks down the neurotransmitter acetylcholine. By blocking this enzyme, DIPF causes an accumulation of acetylcholine in the synapses and leads to muscle paralysis and respiratory failure.
  • Iodoacetamide, a compound that modifies cysteine residues and can be used to identify whether one or more cysteine residues are required for enzyme activity. For example, iodoacetamide can inhibit papain, a cysteine protease that cleaves peptide bonds.
  • Penicillin, an antibiotic that inhibits the transpeptidase enzyme that forms the cross-links in the bacterial cell wall. By binding covalently to a serine residue in the active site of the enzyme, penicillin prevents the formation of a stable peptidoglycan layer and makes the bacteria susceptible to osmotic lysis.