Cytochrome P-450: Difference between revisions

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'''Cytochrome P-450''' is a "superfamily of hundreds of closely related hemeproteins found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (mixed function oxygenases). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of [[steroid]]s, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (biotransformation). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism."<ref>{{MeSH}}</ref>
==Common abnormal alleles==
===CYP2C9===
''CYP2C9'' is an [[isoenzyme]] of cytochrome P-450. [[Genetic polymorphism|Polymorphisms]] of CYP2C9 explain 10% of variation in [[warfarin]] dosing<ref name="pmid15883587">{{cite journal |author=Wadelius M, Chen LY, Downes K, ''et al'' |title=Common VKORC1 and GGCX polymorphisms associated with warfarin dose |journal=Pharmacogenomics J. |volume=5 |issue=4 |pages=262-70 |year=2005 |pmid=15883587 |doi=10.1038/sj.tpj.6500313}}</ref>, mainly among Caucasian patients as these variants are rare in African American and most Asian populations.<ref name="pmid15714076">{{cite journal |author=Sanderson S, Emery J, Higgins J |title=CYP2C9 gene variants, drug dose, and bleeding risk in warfarin-treated patients: a HuGEnet systematic review and meta-analysis |journal=Genet. Med. |volume=7 |issue=2 |pages=97-104 |year=2005 |pmid=15714076 |doi=}}</ref> A [[meta-analysis]] of mainly Caucasian patients found<ref name="pmid15714076"/>:
* CYP2C9*2 allele:
** present in 12.2% of patients
** mean reduction was in warfarin dose was 0.85 mg (17% reduction)
** relative bleeding risk was 1.91
* CYP2C9*3 allele:
** present in 7.9% of patients
** mean reduction was in warfarin dose was 1.92 mg (37% reduction)
** relative bleeding risk was 1.77
===CYP2D6===
===CYP2D6===
3-10% of anglos are poor metabolizers of drugs that use the CYP2D6 [[isoenzyme]].<ref name="pmid11710893">{{cite journal |author=Phillips KA, Veenstra DL, Oren E, Lee JK, Sadee W |title=Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review |journal=JAMA |volume=286 |issue=18 |pages=2270–9 |year=2001 |month=November |pmid=11710893 |doi= |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=11710893 |issn=}}</ref> This affects many [[antidepressant]]s, [[metoprolol]] and other drugs that use this [[isoenzyme]]. More information is available at Entrez Gene.<ref name="urlGene Home">{{cite web |url=http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1565 |title=Entrez Gene: CYP2D6 cytochrome P450, family 2, subfamily D, polypeptide 6 [ Homo sapiens ] |author=Anonymous |authorlink= |coauthors= |date= |format= |work= |publisher=National Library of Medicine |pages= |language= |archiveurl= |archivedate= |quote= |accessdate=2009-01-03}}</ref>
3-10% of anglos are poor metabolizers of drugs that use the CYP2D6 [[isoenzyme]].<ref name="pmid11710893">{{cite journal |author=Phillips KA, Veenstra DL, Oren E, Lee JK, Sadee W |title=Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review |journal=JAMA |volume=286 |issue=18 |pages=2270–9 |year=2001 |month=November |pmid=11710893 |doi= |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=11710893 |issn=}}</ref> This affects many [[antidepressant]]s, [[metoprolol]] and other drugs that use this [[isoenzyme]]. More information is available at Entrez Gene.<ref name="urlGene Home">{{cite web |url=http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1565 |title=Entrez Gene: CYP2D6 cytochrome P450, family 2, subfamily D, polypeptide 6 [ Homo sapiens ] |author=Anonymous |authorlink= |coauthors= |date= |format= |work= |publisher=National Library of Medicine |pages= |language= |archiveurl= |archivedate= |quote= |accessdate=2009-01-03}}</ref>
==References==
<references/>
==External links==
* [http://medicine.iupui.edu/flockhart/ Cytochrome p450 drug-interaction table]

Revision as of 11:42, 3 January 2009

CYP2D6

3-10% of anglos are poor metabolizers of drugs that use the CYP2D6 isoenzyme.[1] This affects many antidepressants, metoprolol and other drugs that use this isoenzyme. More information is available at Entrez Gene.[2]

  1. ↑ Phillips KA, Veenstra DL, Oren E, Lee JK, Sadee W (November 2001). "Potential role of pharmacogenomics in reducing adverse drug reactions: a systematic review". JAMA 286 (18): 2270–9. PMID 11710893. [e]
  2. ↑ Anonymous. Entrez Gene: CYP2D6 cytochrome P450, family 2, subfamily D, polypeptide 6 [ Homo sapiens ]. National Library of Medicine. Retrieved on 2009-01-03.
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