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| '''Enzyme induction''' is a process in which a [[molecule]] (''e.g.'' a drug) [[Induction (biology)|induces]] (''i.e.'' initiates or enhances) the [[gene expression|expression]] of an [[enzyme]].
| | #REDIRECT [[enzyme inhibitor]] |
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| '''Enzyme inhibition''' can refer to
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| * the inhibition of the expression of the enzyme by another molecule
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| * [[Enzyme inhibitor|interference at the enzyme-level]], basically with how the enzyme works. This can be [[competitive inhibition]], [[uncompetitive inhibition]], [[non-competitive inhibition]] or partially competitive inhibition.
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| If the molecule induces enzymes that are responsible for its own [[metabolism]], this is called '''auto-induction''' (or '''auto-inhibition''' if there is inhibition). These processes are particular forms of [[Regulation of gene expression|gene expression regulation]].
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| These terms are of particular interest to [[pharmacology]], and more specifically to [[drug metabolism]] and [[drug interaction]]s. They also apply to [[molecular biology]].
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| In the late 1950s and early 1960s, the French molecular biologists [[François Jacob]] and [[Jacques Monod]] became the first to explain enzyme induction, in the context of the [[lac operon]] of [[Escherichia coli]]. In the absence of lactose, the constitutively expressed [[lac repressor]] protein binds to the operator region of the DNA and prevents the transcription of the operon genes. When present, lactose binds to the lac repressor, causing it to separate from the DNA and thereby enabling transcription to occur. Monod and Jacob generated this theory following 15 years of work by them and others (including [[Joshua Lederberg]]), partially as an explanation for Monod's observation of [[diauxie]]. Previously, Monod had hypothesized that enzymes could physically adapt themselves to new substrates; a series of experiments by him, Jacob, and [[Arthur Pardee]] eventually demonstrated this to be incorrect and led them to the modern theory, for which he and Jacob shared the [[1965]] [[Nobel_Prize_in_Physiology_or_Medicine|Nobel Prize in Physiology or Medicine]] (together with [[André Lwoff]]).<ref>{{cite web|last = Mulligan|first = Martin|title = Induction|url=http://www.mun.ca/biochem/courses/4103/topics/induction.html|accessdate = 2007-01-01}}</ref>
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| ==Cytochrome P450==
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| {{Main|Cytochrome P450#Drug metabolism}}
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| One class of key enzymes for drug metabolism belong to the family of [[cytochrome P450 oxidase]]s, like [[CYP3A4]], [[CYP2D6]], [[CYP1A2]], ''etc''. They reside in the [[endoplasmatic reticulum]] (ER), and prolonged usage of substances inducing enzymes here may cause proliferation of the ER. They are responsible for [[Drug metabolism#Phase I vs. Phase II|phase I reactions]].
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| Enzyme induction and inhibition are important processes to take in account when using drugs of vital importance to the patient, drugs with important [[side effects]] and drugs with small [[therapeutic window]]s, but any drug may be subject to an altered plasma concentration due to altered [[drug metabolism]].
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| A classical example includes [[Anticonvulsant|anti-epileptic drugs]]. [[Phenytoin]], for example, induces [[CYP1A2]], [[CYP2C9]], [[CYP2C19]] and [[CYP3A4]]. Substrates for the latter may be drugs with critical dosage, like [[amiodarone]] or [[carbamazepine]], whose [[blood plasma]] [[concentration]] may decrease because of enzyme induction.
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| Not only drugs may alter drug metabolism. [[Tobacco smoking]] induces [[CYP1A2]] (example substrates are [[clozapine]]/[[olanzapine]]), [[Saint-John's wort]] (a common [[herbal remedy]]) induces [[CYP3A4]], which is inhibited by [[grapefruit juice]]. There are known examples of situations where this may produce clinical effects.
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| ==References==
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| <references/>
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| ==External links==
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| * {{MeshName|Enzymologic+Gene+Expression+Regulation}}
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| [[Category:Pharmacokinetics]]
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| [[Category:Gene expression]]
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| [[de:Enzyminduktion]]
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| [[nl:enzym inductie]]
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