Reversible inhibitors

• An enzyme's activity can be reduced or stopped,?temporarily, by a?reversible inhibitor
• There are?two types?of reversible inhibitors:
  • Competitive?inhibitors have a?similar shape?to that of the?substrate?molecules and therefore?compete?with the substrate for the active site
  • Non-competitive?inhibitors?bind?to the enzyme at an?alternative site, which?alters the shape of the active site?and therefore?prevents?the?substrate?from?binding?to it

   

Competitive and non-competitive inhibition

Reversible inhibitors and reaction rate

• Both types of reversible inhibitors?slow down?or?stop?enzyme activity, decreasing the rate of reaction
• Increasing?the concentration of an inhibitor, therefore,?reduces?the rate of reaction and eventually, if inhibitor concentration continues to be increased, the reaction will?stop completely
• For?competitive inhibitors, countering the increase in inhibitor concentration by?increasing?the?substrate?concentration?can increase the rate of reaction once more (more substrate molecules mean they are more likely to collide with enzymes and form enzyme-substrate complexes)
• For?non-competitive inhibitors, increasing the substrate concentration?cannot?increase the rate of reaction once more, as the shape of the active site of the enzyme remains changed and enzyme-substrate complexes are still unable to form

The effect of inhibitor concentration on the rate of an enzyme-catalysed reaction

End-product inhibition and the control of metabolic pathways

• Reversible inhibitors can act as?regulators?in?metabolic pathways
• Metabolic reactions must be very?tightly controlled?and?balanced, so that no single enzyme can ‘run wild’ and continuously and uncontrollably generate more and more of a particular product
• Metabolic reactions can be?controlled?by using the?end-product?of a particular sequence of metabolic reactions as a?non-competitive, reversible inhibitor:
  • As the enzyme converts the substrate into product, the process is itself?slowed down?as the?end-product?of the reaction chain binds to an alternative site on the original enzyme, changing the shape of the active site and preventing the formation of further enzyme-substrate complexes
  • The end-product can then?detach?from the enzyme and be used elsewhere, allowing the active site to?reform?and the enzyme to return to an?active state
  • This means that as product levels fall, the enzyme begins catalysing the reaction once again, in a continuous?feedback loop
  • This process is known as?end-product inhibition

   

End-product inhibition

Non-reversible inhibitors

• Some inhibitors can form?covalent bonds?with enzymes, inhibiting them?permanently
  • These are known as?non-reversible?or?irreversible inhibitors

   

• If this type of inhibition occurs in a living cell or organism it will result in the?complete inactivation?of the enzyme
  • This can be?dangerous?as can cause the biological reaction the enzyme is catalysing to be?completely stopped
  • The only way to avoid this is for the cell or organism to?produce more of the enzyme?being inhibited, which can only be achieved by transcribing and translating the gene(s) for that enzyme, which is a?relatively slow?process

   

• This is why some non-reversible inhibitors are considered to be?metabolic poisons
• For example,?cyanide?acts as a non-reversible inhibitor of?cytochrome oxidase, a?mitochondrial enzyme?that catalyses one of the key reactions in?aerobic respiration
  • This can be?fatal?as it takes?too long?to produce new enzymes?and the organism will?die?before this can occur
  • As it stops a?metabolic reaction, cyanide is known as a?metabolic poison

   

• Other non-reversible inhibitors, such as?lead?and?mercury, are also serious poisons
  • For example, lead acts as a non-reversible inhibitor of?ferrochelatase, an enzyme involved in the production of?haem?for?haemoglobin

   

• Some non-reversible inhibitors can be?beneficial?if they can be used, in a?medical context, to inhibit enzymes that cause?harm?to some individuals

Examples of Non-reversible Inhibitors as Medicinal drugs