Enzyme Inhibition

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•  Enzyme inhibitors can be competitive or non-competitive

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

enzyme reaction

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

competitive inhibition

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

noncompetitive inhibition

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, RelenzaTM 
  • 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

                            Host Status:         Normal Infection             Treatment with Relenza

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

                            Electron Transport Chain:         Normal Function             Treatment with Cyanide