Enzyme Inhibition (College Board AP Biology)

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

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