7.12
Enzyme Inhibition
Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of i…
Specific chemicals can regulate the action of enzymes by inhibiting, or blocking, their function. Enzyme inhibitors come in two different forms: competitive and non-competitive.
A competitive inhibitor is similar enough to the enzyme's specific substrate that it can bind to the active site and block the substrate from binding. This action essentially decreases the number of enzymes available to bind to the substrate.
In contrast, a non-competitive inhibitor will bind away from, but still influence, the active site by changing the enzyme's shape, for example, and greatly reducing the affinity for the substrate binding to the active site, preventing the enzyme from functioning properly.
In addition, both types of inhibitors differentially affect the rate of a chemical reaction.
Compared to a control, a normal enzymatic reaction rate, a reaction including a competitive inhibitor would take longer to reach Vmax, the maximum reaction rate, and would require more substrate to do so, as there must be enough substrate to consistently outcompete the inhibitor for access to the active sites.
On the other hand, a non-competitive inhibitor would not allow the rate to reach Vmax, because the number of enzymes available for binding is reduced.
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Q1: What is the difference between competitive and non-competitive enzyme inhibitors?
Competitive inhibitors resemble the enzyme's substrate and bind to the active site, blocking substrate access and reducing available enzymes. Non-competitive inhibitors bind to allosteric sites away from the active site, changing the enzyme's shape and reducing substrate affinity. Both types regulate enzyme function but through different mechanisms and with distinct effects on reaction rates.
Q2: How does a competitive inhibitor affect the maximum reaction rate?
A competitive inhibitor does not prevent the enzyme from reaching Vmax, the maximum reaction rate. However, it requires more substrate and longer time to achieve this rate because substrate must outcompete the inhibitor for active site access. With sufficiently high substrate concentrations, the enzyme can still reach its maximum velocity.
Q3: Why can't non-competitive inhibitors be overcome by increasing substrate concentration?
Non-competitive inhibitors bind to allosteric sites and reduce the total number of functional enzymes available. Since they don't occupy the active site, adding more substrate cannot overcome their effect. The enzyme cannot achieve Vmax because the inhibitor permanently reduces the enzyme population capable of catalyzing the reaction.
Q4: What is an example of a competitive inhibitor used as a drug?
Disulfiram is a competitive inhibitor used to treat chronic alcoholism. It binds to the active site of acetaldehyde dehydrogenase, preventing the conversion of acetaldehyde to acetyl coenzyme A. When alcohol is ingested, acetaldehyde accumulates, causing hangover-like symptoms that discourage alcohol consumption.
Q5: How do reversible and irreversible enzyme inhibitors differ in cells?
Reversible inhibitors interact with enzymes through weak interactions and are useful for regulating metabolic processes in normally functioning cells. Irreversible inhibitors form covalent bonds with enzymes, permanently blocking their function. Some toxins use irreversible inhibition, while regulatory inhibitors typically employ reversible binding for metabolic control.
Q6: How do enzyme inhibitors regulate cellular metabolism?
Inhibitors reduce enzyme activity by binding to the enzyme, either at the active site or at allosteric sites. This regulation allows cells to control reaction rates and metabolic pathways. Drugs and toxins can also inhibit enzymes, making inhibition a critical mechanism for both normal cellular function and therapeutic intervention.
Q7: Why are enzyme inhibitors important targets for cancer research?
Cancer cells rely on enzymes regulating cell growth and division. Researchers explore molecules that competitively and non-competitively inhibit these growth-regulating enzymes to block cancer cell proliferation. By targeting specific enzymes with inhibitors, scientists can develop therapies that selectively suppress cancer cell activity while minimizing effects on normal cells.