A wide variety of compounds can reduce enzyme activities. These compounds are called enzyme inhibitors. Enzyme inhibitors bind to the enzyme and reduce their activity. The process is called Enzyme Inhibition.
Enzyme Inhibition Types
There are 3 types of enzyme inhibitions
1. Competitive enzyme inhibition
2. Non Competitive enzyme Inhibition
3. Un Competitive enzyme Inhibition
1. Competitive enzyme inhibition
In competitive enzyme inhibition, the inhibitors is structurally similar to the substrate (substrate analogue). Hence inhibitor competes with the substrate for binding with the active site of enzyme.
The binding of inhibitors to active site of the enzymes prevents the substrate from the binding with enzyme, which results in decrease ES formation and reduced rate of enzyme reaction.
The formation of ES complex or EI complex depends upon the relative concentration of substrate and inhibitors. Competitive enzymes inhibition is reversible. It can be overcome by high substrate concentration. Thus competitive enzyme inhibition does not alter the Vmax, but increase the Km value.
Malonate is the competitive inhibitor of succinate dehydrogenase enzyme. Succinate dehydrogenase enzyme converts succinate to fumurate. Malonate has a structure similar to succinate, hence competes with succinate to bind with succinate dehydrogenase. Hence malanote competitively inhibits succinate dehydrogenase enzyme.
Note: The structure of malonate is similar to succinate. So, Malonate competes with succinate to bind with competitive site of succinate dehydrogenase enzyme, hence competitively inhibits the enzyme.
Biomedical importance of competitive enzyme inhibition:
The mechanism of competitive enzyme inhibition is used in chemotherapy (treatment with the help of chemical compounds) of certain diseases. These are synthetic chemical compounds, which are designed to have structures similar to desired substrates whose reaction needs to be competitively inhibited. These compounds, when ingested, competitively inhibit specific enzymes blocking the unwanted reactions. (Such compounds are referred to as ‘Antimetabolites’).
1) Treatment of gout: Gout is a clinical condition caused due to the increased levels of uric acid in the blood and subsequent accumulation of uric acid in the joints causing severe pain (arthritis). The enzyme xanthine oxidase produces uric acid from hypoxanthine (which in turn is obtained from catabolism of purine nucleotides).
2. Non competitive enzyme inhibition:
In non-competitive enzyme inhibition, the inhibitor is not structurally similar to the substrate, hence does not compete with the substrates for the active site.
Types: Non-competitive enzyme inhibitions can be reversible or irreversible (generally irreversible). But both show similar kinetics.
a) Reversible non competitive enzyme inhibition
In Non-competitive enzyme inhibition, the inhibitor is not structurally similar to the substrate, hence does not compete with the substrates for the active site of the enzyme. The inhibitor may or may not bind with the active site. Instead it may (mostly) bind to the enzyme at a site other than the active site. Since S and I may combine at different sites, formations of both EI and ESI complexes are possible. Since ESI may breakdown to form products at a slower rate than does ES, the reaction may be slowed but not stopped. So Inhibitor does not interfere with the binding of substrate with the enzyme, but it lowers the maximum velocity attainable. So Km value is unchanged, but Vmax is lowered.
1) Anti trypsin, non-competitively inhibits trypsin in reversible manner
2) Trypsin inhibitor present in soybean and ascaris worm
b) Irreversible non competitive enzyme inhibition (Enzyme poisons):
A varlet, of enzyme ‘poisons’, reduces the enzyme activity non-competitively. Here the inhibitor is not structurally similar to the substrate, but these inhibitors generally bind to the active site of enzymes (binds covalently) and inactivate them, which is irreversible. This process is not readily reversible by increasing the substrate concentration; however, the presence of substrates exerts a protective role by blocking or slowing the access of inhibitor to the active site. Usually, these enzyme poisons are not biological compounds.
1) Inhibition of enzymes by heavy metals like Hg+2, Ag+, Pb+2, etc.
2) Inhibition of Enolase (A glycolytic enzyme) by fluoride
3) Inhibition of cytochrome oxidase enzyme by cyanide.
3. Uncompetitive Enzyme Inhibition
In uncompetitive enzyme inhibition, the inhibitors do not bind to free enzymes but can bind only to the ES complex and decrease the velocity of enzymatic reactions. Uncompetitive enzyme inhibitors decrease both Vmax and Km of enzymes.
1. Inhibition of Placental alkaline phosphate enzyme by Phenylalanine
2. Inhibition of S-adenosyl methyl transferase by ATP ( In Yeast )