Competitive inhibitor

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In biochemistry there are three ways in which certain chemical substances may reduce or prevent the activities of enzymes: competitive, non-competitive and uncompetitive inhibition.

In competitive inhibition, the molecule binds to the same active site as the normal enzyme substrate, but doesn't necessarily activate it. The substrate molecules cannot enter the active site while the inhibitor is there, and inhibitors cannot enter the site when the substrate is there. This is classical competitive inhibition. Non-classical inhibition occurs when the inhibitor binds remote to the active site, creating a conformational change in the enzyme such that the substrate can no longer bind to it. Characteristic for this mode of inhibition is that increasing the concentration of substrate reduces the effect of the inhibitor, and vice-versa. In this case, the maximum speed of the reaction is unchanged because though the substrate's affinity for the site is decreased, eventually the substrate concentration will increase to match the concentration of the inhibitor. This is almost complete inhibition.

In noncompetitive inhibition, the inhibitor works by occupying some other site on the enzyme, as in non-classical competitive inhibition. In this case, the enzyme will bind with the inhibitor creating an E-I complex. The substrate will still be allowed to bind to the enzyme, thus creating an E-I-S complexe thereafter. The reaction will still take place when the inhibitor leaves the enzyme, but the speed will be decreased. The Michaelis-Menten constant, Km, which is a measure of the substrate's affinity for the site will remain the same, even though the maximum speed of the reaction decreases. In this mode of inhibition, there is no competition between the inhibitor and the substrate, so increasing the concentration of the substrate still does not allow the maximum enzyme activity rate to be reached.

In uncompetitive inhibition the inhibitor binds only to the E-S complex. The effect is to increase the enzyme's affinity for the substrate, K_m is lowered. This results in decreasing the maximum enzyme activity rate as it takes longer for the substrate/product to leave the active site. Uncompetitive inhibition works best when substrate concentration is high.

In mixed inhibition the inhibitor can bind both to the free enzyme and to the enzyme substrate complex. With this type of inhibition K_m increases and V_max decreases.

The kinetics of these activities is described by the Michaelis-Menten equations. The constant Km is the concentration of the substrate at the point when the speed is at half its maximum value.

Since K_m and V_max can be related to the slopes and intercepts of Lineweaver-Burke and Hanes plots, plotting these graphs for the uninhibited and inhibited reactions can help determine which type of inhibitor is present.

For example, a competitive inhibitor will increase the slope of the Lineweaver-Burke plot while leaving the intercept unchanged.Template:Enzyme-stub

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