Uncompetitive inhibitors are a type of enzyme inhibitor that bind exclusively to the enzyme-substrate complex (ES) rather than the free enzyme. This unique binding mechanism leads to changes in both the Michaelis constant (Km) and the maximum reaction rate (Vmax).
When an uncompetitive inhibitor binds to the ES complex, it prevents the conversion of the substrate into product, effectively reducing the overall reaction rate. This binding stabilizes the ES complex, making it less likely to dissociate back into the free enzyme and substrate. As a result, the apparent affinity of the enzyme for the substrate increases, which is reflected in a decrease in the Km value.
Additionally, because the inhibitor binds to the ES complex, it reduces the amount of active enzyme available to catalyze the reaction. This reduction in active enzyme concentration leads to a decrease in the Vmax, as fewer enzyme molecules are available to convert substrate into product at any given time.
In summary, uncompetitive inhibitors decrease both Km and Vmax because they bind to the enzyme-substrate complex, increasing the apparent affinity of the enzyme for the substrate while simultaneously reducing the overall catalytic efficiency of the enzyme.