Uncompetitive inhibitor

Uncompetitive inhibition, also known as anti-competitive inhibition, takes place when an enzyme inhibitor binds only to the complex formed between the enzyme and the substrate (the E-S complex). Uncompetitive inhibition typically occurs in reactions with two or more substrates or products. Uncompetitive inhibition, also known as anti-competitive inhibition, takes place when an enzyme inhibitor binds only to the complex formed between the enzyme and the substrate (the E-S complex). Uncompetitive inhibition typically occurs in reactions with two or more substrates or products. While uncompetitive inhibition requires that an enzyme-substrate complex must be formed, non-competitive inhibition can occur with or without the substrate present. Uncompetitive inhibition is distinguished from competitive inhibition by two observations: first uncompetitive inhibition cannot be reversed by increasing and second, as shown, the Lineweaver–Burk plot yields parallel rather than intersecting lines. This behavior is found in the inhibition of acetylcholinesterase by tertiary amines (R3N). Such compounds bind to the enzyme in its various forms, but the acyl-intermediate-amine complex cannot break down into enzyme plus product. Uncompetitive inhibition is unique in that the inhibitor binds to the enzyme-substrate complex. This could imply that the binding site for the inhibitor is accessible only after the enzyme has bound to its substrate. As inhibitor binds, the amount of ES complex is reduced. This reduction in the effective concentration of the ES complex can be explained by the fact that having the inhibitor bound to the ES complex essentially converts it to ESI complex, which is considered a separate complex altogether. This reduction in ES complex decreases the maximum enzyme activity (Vmax), as it takes longer for the substrate or product to leave the active site. The reduction in Km - the substrate concentration at which the enzyme can operate at half of its maximal velocity, often used to approximate an enzyme's affinity for a substrate - can also be linked back to the decrease in ES complex. Le Chatelier's principle opposes this decrease and attempts to make up for the loss of ES, so more free enzyme is converted to the ES form, and the amount of ES increases overall. An increase in ES generally indicates that the enzyme has a high degree of affinity for its substrate. Km decreases as affinity for a substrate increases, though it is not a perfect predictor of affinity since it accounts for other factors as well; regardless, this increase in affinity will be accompanied by a decrease in Km.