8.1.2 Inhibition

• Inhibitors are chemical substances that can bind to an enzyme and reduce its activity
• Inhibitors can be formed from within the cell or can be introduced from the external environment
• An enzyme's activity can be reduced or stopped, temporarily, by an inhibitor
• There are two types of inhibitors: competitive and non-competitive

Competitive inhibitors

• Competitive inhibitors have a similar shape to that of the substrate molecules
• They bind to the active site of the enzyme, interfering with it and competing with the substrate for the active site
• The substrate, therefore, cannot bind to the active site if a competitive inhibitor is already bound

Non-competitive inhibitors

• Non-competitive inhibitors bind to the enzyme at an alternative site, which alters the shape of the active site
• This therefore prevents the substrate from binding to the active site

Competitive and non-competitive inhibition

Examples of competitive and non-competitive inhibitors

• An example of a competitive inhibitor involves the enzyme RuBisCo, an important carbon fixation enzyme in photosynthesis
  • Oxygen is a competitive inhibitor to this enzyme and blocks the active site for carbon dioxide
  • Therefore carbon dioxide cannot bind to RuBisCo and reactions involved in photosynthesis slow down or cease to occur
  • This can be fatal to the plant
• An example of a non-competitive inhibitor involves the enzyme cytochrome c oxidase, a mitochondrial enzyme that catalyses one of the key reactions in aerobic respiration
  • Cyanide ions are a non-competitive inhibitor that binds to a site on the enzyme and change the shape of the active site
  • Therefore cytochrome c oxidase cannot carry out its functions in respiration
  • This can be fatal as it takes too long to produce new enzymes and the organism will die before this can occur
  • Cyanide is known as a metabolic poison because it interferes with metabolic pathways

Table comparing competitive and non-competitive inhibitors

• Enzymes can be regulated by chemical substances that bind to a site on the enzyme away from the active site, known as the allosteric site
• Binding to this site, away from the active site forms an allosteric interaction leading to a reversible change in the shape and activity
• Chemicals that regulate the metabolic pathway like this are termed allosteric regulators

• End-product inhibition occurs when the end product from a reaction is present in excess and itself acts as a non-competitive inhibitor of the enzyme
• The end product binds to an allosteric site on the enzyme and causes inhibition of the pathway, so they are referred to as allosteric inhibitors
• Allosteric inhibitors are important to prevent the build-up of intermediate products in a metabolic pathway, as each small step of the pathway may produce a new product
• The product therefore does not accumulate and the pathway can continue
  • An outline of the process is as follows:
    • As the enzyme converts substrate to an end product, the process is itself slowed down as the end-product of the reaction chain binds to an allosteric site on the original enzyme, changing the shape of the active site and preventing the formation of further enzyme-substrate complexes
    • The inhibition of the enzyme means that product levels fall, at which point the enzyme begins catalysing the reaction once again; this is a continuous feedback loop
      • The end-product inhibitor eventually detaches from the enzyme to be used elsewhere; this is what allows the active site to reform and the enzyme to return to an active state

End-product inhibition where the end-product of an enzyme controlled pathway inhibits the starting enzyme and limits the reactions