Enzyme Inhibition – Enzymes Ep 3

An enzyme inhibitor is a molecule that binds to an enzyme and prevents it from catalysing a reaction. In this article we will look at two types of enzyme inhibition – competitive and non-competitive inhibition. Although enzyme inhibitors can sometimes have devastating consequences, some of them are actually quite important. We will look at some examples. Make sure to read my first two articles on enzyme basics and enzyme activity if you are unsure about how enzymes work.

Competitive inhibition

A competitive inhibitor is a molecule which has a very similar shape to the substrate of the enzyme that it inhibits. Because of the similar shape, the inhibitor is able to bind to the active site of the enzyme. When this happens, the active site is blocked and the enzyme can no longer carry out its function. The inhibitor competes with the substrate to bind to the active site. Therefore, as the substrate concentration increases, the substrate is more likely to win. But if the inhibitor concentration increases, the inhibitor is more likely to win. So overall the rate of reaction depends on the relative concentrations of both the substrate and the inhibitor.

A competitive inhibitor binds to the active site

Non-competitive inhibition

A non-competitive inhibitor is a molecule which binds to the enzyme, but not in the active site. Instead, it binds to an allosteric site somewhere else on the enzyme. When the inhibitor binds to the allosteric site, the active site changes shape. The substrate is no longer complementary to the active site, and the reaction cannot be catalysed. So this time it doesn’t matter how much you increase the substrate concentration – the reaction still can’t occur because the enzyme-substrate complex cannot form. However, you will notice on the graph that the maximum rate of reaction is not zero. This is because some of the available enzymes may not be affected by the inhibitor, so they can carry on as normal and bind the substrate. It really depends how much of the inhibitor is present.

A non-competitive inhibitor binds to an allosteric site

Reversible and non-reversible inhibition

Enzyme inhibition (competitive or non-competitive) can be reversible if the inhibitor is only bound to the enzyme with weak bonds such as hydrogen bonds. However, if the inhibitor is bound with strong covalent bonds the inhibition is non-reversible because it is very difficult to break the covalent bonds.

Dangerous enzyme inhibitors

Some metabolic poisons work by inhibiting enzymes that catalyse metabolic reactions. They are particularly devastating if they inhibit respiration. No respiration = no ATP = severe damage or death. Two metabolic poisons you may have heard of are:

  • Arsenic – inhibits pyruvate dehydrogenase which catalyses conversion of pyruvate to acetyl-coA in aerobic respiration.
  • Cyanide – irreversibly inhibits cytochrome c oxidase which is an enzyme needed for oxidative phosphorylation (the last stage of aerobic respiration).

Useful enzyme inhibitors

Many drugs used in medicine are enzyme inhibitors. One example is statins, which are very commonly taken to lower the levels of LDL cholesterol in the blood. They do this by competitively inhibiting an enzyme called HMG-coA reductase which catalyses cholesterol synthesis in the liver. So taking statins reduces the amount of cholesterol the liver produces.

Inhibition can help to regulate metabolic pathways in cells. There are two main types of reversible inhibition that do this:

  • Product inhibition – where the product of a reaction works to inhibit the enzyme that catalyses the reaction. This prevents the reaction from carrying on when there is enough product.
  • End-production inhibition – where the last product in a metabolic pathway works to inhibit an enzyme that catalyses a reaction near the start of the pathway. Again, this controls the amount of end-product that gets produced.

Sometimes enzymes even inhibit themselves. They might be synthesised initially as inactive precursors – proteins which will become the enzyme, but are not yet active and able to bind a substrate. Once part of the inactive precursor gets removed, then it becomes the active enzyme.


  • A competitive enzyme inhibitor is very similar in shape to the substrate and will compete with the substrate to bind to the active site.
  • A non-competitive inhibitor binds to an allosteric site and changes the shape of the active site so the substrate cannot bind.
  • Enzyme inhibition can be reversible or non-reversible depending on how the inhibitor is bound to the enzyme.
  • Specific examples of enzyme inhibitors include metabolic poisons and medicinal drugs.

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