Brent Cornell

    
An enzyme inhibitor is a molecule that disrupts the normal reaction pathway between an enzyme and a substrate

• Enzyme inhibitors can be either competitive or non-competitive depending on their mechanism of action

Types of Enzyme Inhibition

Enzyme inhibitors prevent the formation of an enzyme-substrate complex and hence prevent the formation of product

• Inhibition of enzymes may be either reversible or irreversible depending on the specific effect of the inhibitor being used

Normal Enzyme Reaction

• In a normal reaction, a substrate binds to an enzyme (via the active site) to form an enzyme-substrate complex
• The shape and properties of the substrate and active site are complementary, resulting in enzyme-substrate specificity
• When binding occurs, the active site undergoes a conformational change to optimally interact with the substrate (induced fit)
• This conformational change destabilises chemical bonds within the substrate, lowering the activation energy
• As a consequence of enzyme interaction, the substrate is converted into product at an accelerated rate
  
  

Competitive Inhibition

• Competitive inhibition involves a molecule, other than the substrate, binding to the enzyme’s active site
• The molecule (inhibitor) is structurally and chemically similar to the substrate (hence able to bind to the active site)
• The competitive inhibitor blocks the active site and thus prevents substrate binding
• As the inhibitor is in competition with the substrate, its effects can be reduced by increasing substrate concentration
  
  

Noncompetitive Inhibition

• Non-competitive inhibition involves a molecule binding to a site other than the active site (an allosteric site)
• The binding of the inhibitor to the allosteric site causes a conformational change to the enzyme’s active site
• As a result of this change, the active site and substrate no longer share specificity, meaning the substrate cannot bind
• As the inhibitor is not in direct competition with the substrate, increasing substrate levels cannot mitigate the inhibitor’s effect
  
  

Examples of Enzyme Inhibition

Enzyme inhibitors can serve a variety of purposes, including in medicine (to treat disease) and agriculture (as pesticides)

• An example of a use for a competitive inhibitor is in the treatment of influenza via the neuraminidase inhibitor, Relenza^TM 
• An example of a use for a non-competitive inhibitor is in the use of cyanide as a poison (prevents aerobic respiration)

Relenza (Competitive Inhibitor)

• Relenza is a synthetic drug designed by Australian scientists to treat individuals infected with the influenza virus
• Virions are released from infected cells when the viral enzyme neuraminidase cleaves a docking protein (haemagglutinin)
• Relenza competitively binds to the neuraminidase active site and prevents the cleavage of the docking protein
• Consequently, virions are not released from infected cells, preventing the spread of the influenza virus
  
  

Cyanide (Noncompetitive Inhibitor)

• Cyanide is a poison which prevents ATP production via aerobic respiration, leading to eventual death
• It binds to an allosteric site on cytochrome oxidase – a carrier molecule that forms part of the electron transport chain
• By changing the shape of the active site, cytochrome oxidase can no longer pass electrons to the final acceptor (oxygen)
• Consequently, the electron transport chain cannot continue to function and ATP is not produced via aerobic respiration