Competitive inhibition

Competitive inhibition is a form of enzyme inhibition where binding of the inhibitor to the active site on the enzyme prevents binding of the substrate and vice versa.

Most competitive inhibitors function by binding reversibly to the active site of the enzyme. As a result, many sources state that this is the defining feature of competitive inhibitors. This, however, is a misleading oversimplification, as there are many possible mechanisms by which an enzyme may bind either the inhibitor or the substrate but never both at the same time. For example, allosteric inhibitors may display competitive, non-competitive, or uncompetitive inhibition.

Mechanism

In competitive inhibition, at any given moment, the enzyme may be bound to the inhibitor, the substrate, or neither, but it cannot bind both at the same time.

In virtually every case, competitive inhibitors bind in the same binding site as the substrate, but same-site binding is not a requirement. A competitive inhibitor could bind to an allosteric site of the free enzyme and prevent substrate binding, as long as it does not bind to the allosteric site when the substrate is bound. For example, strychnine acts as an allosteric inhibitor of the glycine receptor in the mammalian spinal cord and brain stem. Glycine is a major post-synaptic inhibitory neurotransmitter with a specific receptor site. Strychnine binds to an alternate site that reduces the affinity of the glycine receptor for glycine, resulting in convulsions due to lessened inhibition by the glycine.

Non-competitive inhibition

Non-competitive inhibition is a type of enzyme inhibition where the inhibitor reduces the activity of the enzyme and binds equally well to the enzyme whether or not it has already bound the substrate.

The inhibitor may bind to the enzyme whether or not the substrate has already been bound, but if it has a higher affinity for binding the enzyme in one state or the other, it is called a mixed inhibitor.

Terminology

It is important to note that while all non-competitive inhibitors bind the enzyme at allosteric sites (i.e. locations other than its active site)—not all inhibitors that bind at allosteric sites are non-competitive inhibitors. In fact, allosteric inhibitors may act as competitive, non-competitive, or uncompetitive inhibitors.

Many sources continue to conflate these two terms, or state the definition of allosteric inhibition as the definition for non-competitive inhibition.

Mechanism

Non-competitive inhibition models a system where the inhibitor and the substrate may both be bound to the enzyme at any given time. When both the substrate and the inhibitor are bound, the enzyme-substrate-inhibitor complex cannot form product and can only be converted back to the enzyme-substrate complex or the enzyme-inhibitor complex. Non-competitive inhibition is distinguished from general mixed inhibition in that the inhibitor has an equal affinity for the enzyme and the enzyme-substrate complex.