Enzyme inhibitors function as an important mechanism for regulating enzymatic activity.
The cell uses specific molecules to regulate enzymes in order to promote or inhibit certain chemical reactions. Sometimes it is necessary to inhibit an enzyme to reduce a reaction rate, and there is more than one way for this inhibition to occur. In competitive inhibition, an inhibitor molecule is similar enough to a substrate that it can bind to the enzyme’s active site to stop it from binding to the substrate. It “competes” with the substrate to bind to the enzyme.
In noncompetitive inhibition, an inhibitor molecule binds to the enzyme at a location other than the active site (an allosteric site). The substrate can still bind to the enzyme, but the inhibitor changes the shape of the enzyme so it is no longer in an optimal position to catalyze the reaction.
Mixed inhibitors bind at a site on the enzyme other than the active site, so they do not prevent the substrate from binding. Their name is inspired by the fact that they can bind to either the enzyme alone or the enzyme-substrate complex. Most types of mixed inhibitors have a preference for one or the other, which dictates the effect on Km and Vmax. Mixed inhibitors that act like competitive inhibitors by binding primarily to the enzyme before the substrate is associated increase Km (like competitive inhibitors). In contrast, mixed inhibitors that act more like uncompetitive inhibitors by preferring to bind to the enzyme-substrate complex lower Km. All mixed inhibitors lover Vmax to some extent.
Uncompetitive inhibitors bind at a site other than the active site. Regulatory molecules can also bind to a site other than the active site and exert a positive feedback effect (as opposed to an inhibitory effect). Uncompetitive inhibitors do not bind to the enzyme until it has associated with the substrate to form the enzyme-substrate complex. Once the uncompetitive inhibitor has bound, the substrate remains associated with the enzyme. The apparent affinity of the enzyme for the substrate increases, meaning that Km decreases. Because the uncompetitive inhibitor only affects enzymes that have already bound the substrate, adding more substrate does not overcome the effect of the inhibitor. The Vmax is lowered because the substrate stays bound to the enzyme for a longer period of time. Uncompetitive inhibitors decrease the Vmax and Km proportionally.
Characteristics of Enzyme Inhibitors
|Type of Inhibitor||Binding Site||Inhibits Binding of Substrate?||Effect on Km||Effect on Vmax|
|Competitive||Enzyme (active site)||Yes||Increase||No change|
|Mixed||E-S complex or enzyme||No||Increase OR decrease||Decrease|
|Noncompetitive||E-S complex or enzyme||No||No change||Decrease|
Graphing experimental data from reactions with and without an inhibitor in a Lineweaver-Burk plot allows for the identification of the type of inhibition, based on how the best-fit line changes. Then the changes in Km and Vmax can be calculated. For example, a competitive inhibitor will change the Km, but not the Vmax – so the slope and x-intercept of the Lineweaver-Burk plot will be different from the original reaction but the y-interecept (Vmax) will remain the same. The addition of an uncompetitive inhibitor decreases both the Km and Vmax, but it does so proportionally such that the slope of the Lineweaver-Burk plot (Km/Vmax) does not change.
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• In competitive inhibition, an inhibitor molecule competes with a substrate by binding to the enzyme ‘s active site so the substrate is blocked.
• In noncompetitive inhibition (also known as allosteric inhibition), an inhibitor binds to an allosteric site; the substrate can still bind to the enzyme, but the enzyme is no longer in optimal position to catalyze the reaction.
• Mixed inhibitors bind at a site on the enzyme other than the active site, so they do not prevent the substrate from binding. Their name is inspired by the fact that they can bind to either the enzyme alone or the enzyme-substrate complex.
• Uncompetitive inhibitors bind at a site other than the active site. Uncompetitive inhibitors do not bind to the enzyme until it has associated with the substrate to form the enzyme-substrate complex.
allosteric site: a site other than the active site on an enzyme.
noncompetitive inhibition: inhibitor molecules bind to the enzyme at a location other than the active site
competitive inhibition: an inhibitor molecule is similar enough to a substrate that it can bind to the enzyme’s active site to stop it from binding to the substrate
substrate: a reactant in a chemical reaction is called a substrate when acted upon by an enzyme
inhibitor: a molecule that binds to an enzyme and decreases its activity
Vmax: The maximal velocity, or rate of a reaction, at saturating substrate concentrations.
Km: the michaelis constant is a measure of the affinity of the enzyme for the substrates
positive feedback: is a process that occurs in a feedback loop which exacerbates the effects of a small disturbance
affinity: how strongly an enzyme binds to a substrate
Lineweaver-Burk plot: A method for experimentally determining the kinetic parameters of an enzymatic reaction. The slope is equal to Km/Vmax.