How does increasing substrate concentration affect noncompetitive inhibition?

• 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, 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
  
  

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)

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  What will happen if you increase the substrate concentration in competitive inhibition?

  The V_max of the enzyme-catalyzed reaction in the presence of a competitive inhibitor remains unchanged from normal; however, the apparent K_m (K_m') for the substrate is increased since a higher concentration of substrate is required to overcome inhibitory effects of the competitor.

  How does substrate concentration affect inhibition?

  Substrate concentration affects the primary rate and yield of enzymatic hydrolysis. High substrate concentrations can result in substrate inhibition, which significantly lowers the hydrolysis rate [40].