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Enzyme inhibitors are chemicals that interfere with an enzyme’s catalytic function, slowing or stopping catalysis in some situations. Competitive, non-competitive, and substrate inhibition are the three most common kinds of enzyme inhibition.
The existence of the enzyme-substrate complex ES is at the heart of most inhibition theories. The existence of transient ES structures has been confirmed in the laboratory.
Competitive inhibition occurs when both the substrate and a chemical that looks like the substrate are given to the enzyme. The ‘lock-key theory’ of enzyme catalysts can be used to explain why inhibition occurs.
The concept of an ‘active site’ is used in the lock and key theory. According to this theory, one area of the enzyme’s surface has a great affinity for the substrate. The substrate is held in such a way that it is more easily converted to reaction products. If we take the enzyme to be the lock and the substrate to be the key, the key is inserted into the lock, the door is opened, and the reaction begins.
When an inhibitor that looks like the substrate is present, it will compete with the substrate for the enzyme lock position. When the inhibitor prevails, it takes control of the lock but is unable to unlock it.
As a result, the observed process is slowed because the inhibitor has taken up part of the accessible enzyme sites. If a foreign substance is present that isn’t compatible with the site, the enzyme rejects it, accepts the substrate, and the reaction continues properly.
Non-competitive inhibitors are substances that, when added to an enzyme, cause the enzyme to become incapable of accepting the substrate.
Hence, the observed reaction is slowed down because some of the available enzyme sites are occupied by the inhibitor. If a dissimilar substance that does not fit the site is present, the enzyme rejects it, accepts the substrate, and the reaction proceeds normally.
Non-competitive inhibitors are considered to be substances that, when added to the enzyme, alter the enzyme in a way that it cannot accept the substrate.
Types of enzymatic inhibitors
Competitive inhibition
The substrate and inhibitor cannot bind to the enzyme at the same time in competitive inhibition. This is mainly due to the inhibitor’s affinity for an enzyme’s active site, where the substrate also binds; the substrate and inhibitor compete for access to the active site.
This form of inhibition can be circumvented by using high enough substrate concentrations (Vmax remains constant), i.e. out-competing the inhibitor. However, because it requires a larger concentration of the substrate to reach the Km point, or half the Vmax, the apparent Km will rise. Competitive inhibitors are frequently structurally identical to the true substrate.
Uncompetitive inhibition
The substrate and inhibitor cannot bind to the enzyme at the same time in uncompetitive inhibition. This is mainly due to the inhibitor’s affinity for an enzyme’s active site, where the substrate also binds. The substrate and inhibitor compete for access to the active site. This form of inhibition can be circumvented by using high enough substrate concentrations (Vmax remains constant), i.e. out-competing the inhibitor. However, because it requires a larger concentration of the substrate to reach the Km point, or half the Vmax, the apparent Km will rise. Competitive inhibitors are frequently structurally identical to the true substrate.
Non-competitive inhibition
The binding of the inhibitor to the enzyme decreases its activity but has no effect on substrate binding in non-competitive inhibition. As a result, the extent of inhibition is solely determined by the inhibitor’s concentration. Due to the inability of the reaction to run as efficiently, Vmax will decrease, but Km will remain unchanged because the actual binding of the substrate will, by definition, continue to work normally.
Mixed inhibition
In mixed inhibition, the inhibitor and the enzyme’s substrate both can bind to the enzyme. However, the inhibitor’s binding impacts the substrate’s binding and vice versa.
This type of inhibition can be reduced but not eliminated by increasing substrate concentrations. Although mixed-type inhibitors can bind in the active site, the majority of inhibition is due to an allosteric effect, in which the inhibitor binds to a different spot on the enzyme.
The function of enzyme inhibitors
By affecting the enzyme’s catalytic characteristics and blocking its active site, enzyme inhibitors reduce its activity.
A reaction catalysed by enzymes is slowed down.
Cells use inhibitors as a regulatory mechanism.
Role of enzyme inhibitors
Enzymes don’t inhibit catalytic reactions as the basic purpose of an enzyme is to catalyse reactions. Instead, inhibitors slow down or completely stop the function of an enzyme. Enzymes have active sites which allow certain substrates to fit (thus breaking apart or putting together substrates). Enzymes can have more than one active site and can also have other areas that allow ‘foreign’ molecules to achieve other tasks.
There are two types of inhibitors: competitive and non-competitive inhibitors. Competitive inhibitors have a chemical structure similar to that of an enzyme’s normal substrate allowing it to fit in the enzyme’s active site. The difference is that it doesn’t break apart like normal substrates, thus stopping that active site from catalysing any more reactions. These inhibitors are usually temporary and will move out of the active site through specific triggers.
The maximum rate of reactor will be reached, but a lot slower as competitive inhibitors ‘replace’ substrates. The word ‘competitive’ refers to the fact that it competes with the actual substrate slowing down the catalysing.
Non-competitive inhibitors, on the other hand, don’t bind to the active site but rather to another site on the enzyme. When it is bound to an enzyme, it will change the shape of the enzyme’s active site, meaning that substrates can no longer fit in it and thus won’t be catalysed (denaturing the enzyme). It is usually permanent.
The number of free enzymes is the limiting factor in the maximum rate of reaction. So, if the enzyme takes out some of these enzymes, it will decrease the maximum rate of reaction. Competitive inhibitors have the same Vmax (maximum rate of reaction) because it competes with the substrate. This means that if the number of substrate molecules far exceeds the number of competitive inhibitors, the inhibitors will never even get a chance to get to the enzyme due to the sheer number of substrates. These substrates will use up all the space on the active site. Non-competitive inhibitors are called that because they don’t compete with inhibitors but instead bind to the enzyme through an ‘exclusive’ site.
The body uses inhibitors to control processes in our body, like the metabolic processes. Sometimes the products of these processes can be inhibitors for enzymes in the process, so the more products made, the slower the process.
Conclusion
Enzyme inhibitors can be found in nature or synthesised in a laboratory. Enzyme inhibitors are naturally occurring enzyme inhibitors that are necessary for survival and regulate a range of metabolic activities. Furthermore, naturally occurring poisons are typically enzyme inhibitors that have evolved to make predators, prey, and competitive species toxic. These natural poisons contain some of the most lethal substances on the earth.
Artificial inhibitors include insecticides like malathion, herbicides like glyphosate, and disinfectants like triclosan. Other synthetic enzyme inhibitors block the enzyme acetylcholinesterase, which breaks down acetylcholine, and are used as nerve agents in chemical warfare.
