Professional Documents
Culture Documents
HSP201-0003/2023
ENZYME INHIBITION
Enzyme inhibition is the process by which chemical substances, known as inhibitors inactivate the enzymes hence
hindering the activity of the enzymes. Inhibitors can be organic substances or small inorganic ions.
Enzyme inhibition can be classified into four major categories;
1. Competitive inhibition
2. Non-competitive inhibition
3. Uncompetitive inhibition
4. Allosteric inhibition
1.Competitive inhibition
This is a type of inhibition where the active or catalytic site of the enzyme is occupied by another substance other
than the substrate, hence the catalytic activity of the enzyme is hindered. This type of inhibition is usually reversible.
In such a type of inhibition, both the enzyme-substrate and enzyme-inhibitor complexes are formed during the
reaction, though in different amounts. The actual amounts of the ES AND EI formed depend on various factors such
as;
i. Affinity between the enzyme and the substrate or the inhibitor
ii. Actual concentration of the substrate and the inhibitor present
iii. Time of pre-incubation of the enzyme with the substrate or the inhibitor.
The affinity of the substrate for the enzyme decreases with increase in concentration of the inhibitor this lowering the
enzymatic reaction. Thus, the KM is high but the Vmax is the same in competitive inhibition. This type of inhibition
can be reversed by increasing the concentration of the substrate which will force the inhibitor out of the enzyme-
inhibitor complex.
2. Non-competitive Inhibition
This is of two different types namely reversible and irreversible.
This occurs when the substances not resembling the geometry of the substrate do not exhibit mutual competition.
Most probably the sites of attachment of the substrate and inhibitor are different. The inhibitor binds reversibly with a
site on enzyme other than the active site. So the inhibitor may combine with both free enzyme and ES complex. This
probably brings about the changes in 3D structure of the enzyme inactivating it catalytically. In noncompetitive
inhibition Vmax is lowered, but Km is kept constant. If the inhibitor can be removed from its site of binding without
affecting the activity of the enzyme, it is called as Reversible-Non-competitive Inhibition. However, if the inhibitor can
be removed only at the loss of enzymatic activity, it is known as Irreversible Non-competitive Inhibition. However, the
kinetic properties in case of both are the same.
• Disulfiram (Antabuse): Used in treatment of alcoholism, the drug irreversibly inhibits the enzyme
aldehyde dehydrogenase preventing further oxidation of acetaldehyde which accumulates and produces
sickening effect leading to aversion to alcohol.
• Di-isopropyl fluorophosphate (DFP): Inhibits enzymes with serine in their active site e.g. acetylcholine
esterase
3.Uncompetitive inhibition
Uncompetitive inhibition, also known as anti-competitive inhibition, takes place when an enzyme inhibitor binds only
to the complex formed between the enzyme and the substrate (the ES complex). Uncompetitive inhibition typically
occurs in reactions with two or more substrates or products. While uncompetitive inhibition requires that an enzyme-
substrate complex must be formed, non-competitive inhibition can occur with or without the substrate present.
Uncompetitive inhibition is distinguished from competitive inhibition by two observations: first uncompetitive inhibition
cannot be reversed by increasing [S] and second, as shown, the Lineweaver–Burk plot yields parallel rather than
intersecting lines.
4.Allosteric inhibition
This is a type of inhibition where a ligand binds to one sub unit of an enzyme thus interfering with its catalytic activity.
e. Allosteric inhibition does not follow the Michaelis-Menten hyperbolic kinetics. Instead it gives a
sigmoid kinetics (Fig. 9.13). Allosteric inhibitors shift the substrate saturation curve to the right.
However as opposite to inhibitors, the presence of activators shifts the curve to the left. Types: Allosteric
enzymes are of K and M series according to their kinetics.
• In K-enzymes, e.g. aspartate carbamylate and phosphofructokinase, the allosteric inhibitor lowers the substrate
affinity to raise the Km of the enzyme; but the Vmax is unchanged.
• In M-enzymes, e.g. acetyl-CoA carboxylase, the allosteric inhibitor reduces the maximum velocity but no change in
Km or substrate affinity. Allosteric activators produce a fall in K enzymes and a rise in Vmax in M enzymes.
• When the final product allosterically inhibits the enzyme, it is called as feedback allosteric inhibition.