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| {{distinguish|Uncompetitive inhibitor}}
| | Greetings. Let me start by telling you the writer's title - Phebe. Bookkeeping is what I do. Puerto Rico is where he's been residing for many years and he will never transfer. The preferred hobby for my kids and me is to play baseball and I'm attempting to make it a occupation.<br><br>Have a look at my blog post [http://www.1a-pornotube.com/user/GCalvert http://www.1a-pornotube.com/user/GCalvert] |
| {{redirects|Non-competitive||Competition}}
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| '''Non-competitive inhibition''' is a type of [[Enzyme inhibitor|enzyme inhibition]] where the inhibitor reduces the activity of the enzyme and binds equally well to the enzyme whether or not it has already bound the substrate.<ref name=NIH_Inhibition>{{cite web|title=Types of Inhibition|url=http://assay.nih.gov/assay/index.php/Types_of_Inhibition|accessdate=2 April 2012}}</ref> | |
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| If the inhibitor may bind to the enzyme whether or not the substrate has already been bound, but has a higher affinity for binding the enzyme in one state or the other, it is called a [[mixed inhibition|mixed inhibitor]].<ref name=NIH_Inhibition />
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| == Terminology ==
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| It is important to note that, while all non-competitive inhibitors bind at [[allosteric site]]s—i.e. any site on the enzyme other than its [[active site]]—not all inhibitors that bind at allosteric sites are non-competitive inhibitors.<ref name=NIH_Inhibition /><ref name=classof1>{{cite web|title=Non Competitive Inhibitors|url=http://classof1.com/homework_answers/biochemical_engineering/non_competitive_inhibitors/}}</ref> In fact, allosteric inhibitors may act as [[competitive inhibition|competitive]], non-competitive, or [[uncompetitive inhibition|uncompetitive]] inhibitors.<ref name=NIH_Inhibition />
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| Many sources continue to conflate these two terms,<ref>{{cite web|title=Noncompetitive inhibition and allosteric inhibition|url=http://www.biology-online.org/biology-forum/about15032.html?hilit=Oscillates|publisher=Biology Online (forum)|accessdate=2 April 2012}}</ref><ref>{{cite web|title=Noncompetitive Inhibition|url=http://cti.itc.virginia.edu/~cmg/Demo/noncInh.html|accessdate=2 April 2012}}</ref> or state the definition of allosteric inhibition as the definition for non-competitive inhibition.
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| == Mechanism ==
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| [[File:Non-competitive inhibition.svg|thumb|right|Illustration of a possible mechanism of non-competitive or mixed inhibition.]]
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| Non-competitive inhibition models a system where the inhibitor and the substrate may both be bound to the enzyme at any given time. When both the substrate and the inhibitor are bound, the enzyme-substrate-inhibitor complex cannot form product and can only be converted back to the enzyme-substrate complex or the enzyme-inhibitor complex. Non-competitive inhibition is distinguished from general mixed inhibition in that the inhibitor has an equal affinity for the enzyme and the enzyme-substrate complex.
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| The most common mechanism of non-competitive inhibition involves reversible binding of the inhibitor to an [[Allosteric regulation|allosteric site]], but it is possible for the inhibitor to operate via other means including direct binding to the active site. It differs from competitive inhibition in that the binding of the inhibitor does not prevent binding of substrate, and vice versa, it simply prevents product formation for a limited time.
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| This type of inhibition reduces the [[Chemical kinetics|maximum rate]] of a [[chemical reaction]] without changing the apparent binding [[Dissociation constant#Protein-ligand binding|affinity]] of the [[catalysis|catalyst]] for the [[Substrate (biochemistry)|substrate]] (K<sub>m</sub><sup>app</sup> – see [[Michaelis-Menten kinetics]]).
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| == Equation ==
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| In the presence of a non-competitive inhibitor, the apparent enzyme affinity is equivalent to the actual affinity. In terms of [[Michaelis-Menten kinetics]], [[Michaelis–Menten_kinetics#Michaelis_constant_KM|K<sub>m</sub><sup>app</sup>]] = K<sub>m</sub>. This can be seen as a consequence of [[Le Chatelier's Principle]] because the inhibitor binds to both the enzyme and the enzyme-substrate complex equally so that the equilibrium is maintained. However, since some enzyme is always inhibited from converting the substrate to product, the effective enzyme concentration is lowered.
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| Mathematically,
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| : <math> V_{max}^{app} = \frac{V_{max}}{1+\frac{[I]}{K_I}}</math>
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| : <math> {apparent\ [E]_0} = \frac{[E]_0}{1+\frac{[I]}{K_I}}</math>
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| == Example: noncompetitive inhibitors of CYP2C9 enzyme ==
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| 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>
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| == References ==
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| {{reflist}}
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| # {{Citation
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| |last = Berg
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| |first = Jeremy M.
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| |last2 = Tymoczko
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| |first2 = John L.
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| |last3 = Stryer
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| |first3 = Lubert
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| |authorlink3 = Lubert Stryer
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| |title = Biochemistry
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| |year = 2000
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| |place = [[New York]]
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| |edition = 5th
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| |publisher = WH Freeman & Co.
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| |isbn = 0-7167-6766-X
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| }}
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| {{Enzyme inhibition}}
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| [[Category:Enzymes]]
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| [[Category:Metabolism]]
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| [[Category:Enzyme inhibitors]]
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| [[Category:Pharmacology]]
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Greetings. Let me start by telling you the writer's title - Phebe. Bookkeeping is what I do. Puerto Rico is where he's been residing for many years and he will never transfer. The preferred hobby for my kids and me is to play baseball and I'm attempting to make it a occupation.
Have a look at my blog post http://www.1a-pornotube.com/user/GCalvert