View source for Non-competitive inhibition

'''Non-competitive inhibition''' is a type of [[Enzyme inhibitor|enzyme inhibition]] where the inhibitor reversibly binds to an allosteric site, a site different than the active site, on the enzyme, preventing the substrate from being able to bind to the active site. This type of inhibition reduces the [[Chemical kinetics|maximum rate]] of a [[chemical reaction]] (V<sub>max</sub>) without changing the apparent binding [[Dissociation constant#Protein-ligand binding|affinity]] of the [[catalysis|catalyst]] for the [[Substrate (biochemistry)|substrate]] (K<sub>mApp</sub> in the case of [[enzyme]] inhibition, &ndash; see [[Michaelis-Menten kinetics]]).

Non-competitive inhibition usually applies to [[enzyme]]s and differs from [[competitive inhibition]] in that the inhibitor always binds to the enzyme at a site other than the enzyme's [[active site]] (this other site is called an [[Allosteric regulation|allosteric]] site). This affects the rate of the reaction [[catalysis|catalysed]] by the enzyme because the presence of the inhibitor causes a change in the [[protein structure|structure]] and shape of the enzyme. This change in shape means the enzyme is no longer able to bind with a [[substrate (biochemistry)|substrate]] correctly (See [[Enzymes#.22Lock and key.22 hypothesis|lock and key hypothesis]]). This reduces the concentration of 'active' enzyme resulting in a decrease in the V<sub>max</sub>.  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.

== Note ==
Although non-competitive inhibition generally implies that the inhibitor does not bind to the active site of the enzyme, the converse is not true:  [[Competitive inhibition]] can either be due to competition for the binding site, or by allosteric competitive inhibition. 
For simple Michaelis-Menten kinetics, the apparent maximum reaction rate is as follows:

<math>{apparent\ k}_2=\frac{k_2}{1+\frac{[I]}{K_I}}</math>


<math>V_{max}=k_2[E_0]=\frac{k_2 \times E_0}{1+\frac{[I]}{K_I}}</math>

== Example: noncompetitive inhibitors of [[CYP2C9]] [[enzyme]]  ==
Noncompetitive inhibitors of [[CYP2C9]] [[enzyme]] include [[nifedipine]], [[tranylcypromine]], [[phenethyl isothiocyanate]], and 6-hydroxyflavone. Computer docking simulation and constructed mutants substituted indicate that the noncompetitive binding site of 6-hydroxyflavone is the reported allosteric binding site of [[CYP2C9]] [[enzyme]]<ref>Si Dayong, Wang Y, Guo Y, Wang J, Zhou H, Zhou Y-H, Li Z-S, Fawcett JP (2008). Mechanism of CYP2C9 inhibition by flavones and flavonols. Drug Metabolism and Disposition. doi:10.1124/dmd.108.023416[http://p4502c.googlepages.com/dmd2.pdf]</ref>.

==References==
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{{Enzyme inhibition}}

[[Category:Enzymes]]
[[Category:Metabolism]]
[[Category:Enzyme inhibitors]]
[[Category:Pharmacology]]

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[[Category:2Fix]]