CYP2A6: Difference between revisions

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{{Infobox_gene}}
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{{GNF_Protein_box
| image = PBB_Protein_CYP2A6_image.jpg
| image_source = [[Protein_Data_Bank|PDB]] rendering based on 1z10.
| Name = Cytochrome P450, family 2, subfamily A, polypeptide 6
| HGNCid = 2610
| Symbol = CYP2A6
| AltSymbols =; CYP2A; P450C2A; P450PB; CPA6; CYP2A3; CPA7; CPAD; CYPIIA7; P450-IIA4
| OMIM = 122720
| ECnumber = 
| Homologene = 86656
| MGIid = 
| Function = {{GNF_GO|id=GO:0005506 |text = iron ion binding}} {{GNF_GO|id=GO:0008389 |text = coumarin 7-hydroxylase activity}} {{GNF_GO|id=GO:0019825 |text = oxygen binding}} {{GNF_GO|id=GO:0020037 |text = heme binding}} {{GNF_GO|id=GO:0046872 |text = metal ion binding}} {{GNF_GO|id=GO:0050381 |text = unspecific monooxygenase activity}}
| Component = {{GNF_GO|id=GO:0005783 |text = endoplasmic reticulum}} {{GNF_GO|id=GO:0005792 |text = microsome}} {{GNF_GO|id=GO:0016020 |text = membrane}}
| Process = {{GNF_GO|id=GO:0006118 |text = electron transport}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 1548
    | Hs_Ensembl = 
    | Hs_RefseqProtein = NP_000753
    | Hs_RefseqmRNA = NM_000762
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 
    | Hs_GenLoc_start = 
    | Hs_GenLoc_end = 
    | Hs_Uniprot = 
    | Mm_EntrezGene = 
    | Mm_Ensembl = 
    | Mm_RefseqmRNA = 
    | Mm_RefseqProtein = 
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 
    | Mm_GenLoc_start = 
    | Mm_GenLoc_end = 
    | Mm_Uniprot = 
  }}
}}
{{SI}}


'''Cytochrome P450 2A6''' (abbreviated '''CYP2A6''') is a member of the [[cytochrome P450]] mixed-function oxidase system, which is involved in the metabolism of [[xenobiotic]]s in the body. CYP2A6 is the primary enzyme responsible for the oxidation of [[nicotine]] and [[cotinine]]. It is also involved in the metabolism of several pharmaceuticals, carcinogens, and a number of coumarin-type alkaloids. CYP2A6 is the only enzyme in the human body that appreciably catalyzes the 7-hydroxylation of [[coumarin]], such that the formation of the product of this reaction, 7-hydroxycoumarin, is used as a probe for CYP2A6 activity.


'''Cytochrome P450 2A6''' (abbreviated '''CYP2A6''') is a member of the [[cytochrome P450]] mixed-function oxidase system, which is involved in the metabolism of [[xenobiotic]]s in the body. CYP2A6 is the primary enzyme responsible for the oxidation of [[nicotine]] and [[cotinine]]. It is also involved in the metabolism of several pharmaceuticals, carcinogens, and a number of coumarin-type alkaloids. CYP2A6 is the only enzyme in the human body that appreciably catalyzes the 7-hydroxylation of [[coumarin]], such that the formation of the product of this reaction, 7-hydroxycoumarin, is used as a probe for CYP2A6 activity.
The CYP2A6 gene is part of a large cluster of cytochrome P450 genes from the CYP2A, CYP2B and CYP2F subfamilies on chromosome 19q. The gene was formerly referred to as CYP2A3; however, it has been renamed CYP2A6.<ref>{{cite web | title = Entrez Gene: CYP2A6 cytochrome P450, family 2, subfamily A, polypeptide 6| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1548| accessdate = }}</ref>


The CYP2A6 gene is part of a large cluster of cytochrome P450 genes from the CYP2A, CYP2B and CYP2F subfamilies on chromosome 19q. The gene was formerly referred to as CYP2A3; however, it has been renamed CYP2A6.<ref>{{cite web | title = Entrez Gene: CYP2A6 cytochrome P450, family 2, subfamily A, polypeptide 6| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1548| accessdate = }}</ref>
== Interactive pathway map ==
{{FluoropyrimidineActivity WP1601|highlight=CYP2A6}}


==Distribution==
==Distribution==
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==Induction==
==Induction==
CYP2A6 is known to be [[Enzyme induction and inhibition|inducible]] by [[phenobarbital]] and [[rifampicin]], and it is suspected that other antiepileptic drugs may also have this effect.
CYP2A6 is known to be [[Enzyme induction and inhibition|inducible]] by [[phenobarbital]] and [[rifampicin]], and it is suspected that other antiepileptic drugs may also have this effect.
{{Clear}}


==CYP2A6 Ligands==
==CYP2A6 Ligands==
Line 68: Line 27:
*Many [[Carcinogen]]s
*Many [[Carcinogen]]s
** [[MNAN]]  
** [[MNAN]]  
** [[NNK]] ([[procarcinogen]])
** [[NNK]]  
** [[N-Nitrosodiethylamine|NDEA]] ([[carcinogen]])
** [[N-Nitrosodiethylamine|NDEA]]  
** [[MTBE]] ([[carcinogen]])
** [[MTBE]]  
*Other [[toxin]]s
*Other [[toxin]]s
** [[aflatoxin]] B<sub>1</sub> ([[mycotoxin]])
** [[aflatoxin]] B<sub>1</sub> ([[mycotoxin]])
** [[1,3-butadiene]] (in synthetic rubber)
** [[1,3-butadiene]] (in synthetic rubber)
** [[coumarin]]
** [[coumarin]] ([[anticoagulant]], found in [[cinnamon]])
** [[DCBN]] ([[herbicide]])
** [[DCBN]] ([[herbicide]])
** 7-ethoxycoumarin (test substrate)
** [[7-ethoxycoumarin]] (test substrate)
** [[skatole]]
** [[skatole]]
** [[quinoline]]
** [[quinoline]]
Line 87: Line 46:
* [[SM-12502]] ([[platelet-activating factor|PAF]] [[receptor antagonist|antagonist]]
* [[SM-12502]] ([[platelet-activating factor|PAF]] [[receptor antagonist|antagonist]]
* [[valproic acid]] ([[anticonvulsant]], [[mood-stabilizing]])
* [[valproic acid]] ([[anticonvulsant]], [[mood-stabilizing]])
* [[paracetamol]] ([[analgesic]], [[antipyretic]])
* [[dexmedetomidine]] ([[sedative]])<ref name=":0">{{Cite book|title=Cytochrome P450 Enzymes: Substrates, Inhibitors, and Inducers|vauthors=Lacy CF, Armstrong LL, Goldman MP, Lance LL |publisher=LexiComp Inc|year=2007|isbn=|location=Hudson, OH|pages=1899–1912}}</ref>


||
||
* ([[grapefruit]] juice [[flavonoids]])
* [[amiodarone]] ([[antiarrhythmic agent]])<ref name=":0" />
* [[ketoconazole]] ([[antifungal]])
* [[amlodipine]] ([[calcium channel blocker]])<ref name=":0" />
* [[methoxsalen]] (in [[psoriasis]])
* [[buprenorphine]] ([[Opioid|semisynthetic opioid]])<ref name=":0" />
* [[pilocarpine]] ([[muscarinic receptor]] agonist)
* [[clofibrate]] ([[fibrate]])<ref name=":0" />
* [[tranylcypromine]] ([[antidepressant]])
* [[clotrimazole]] ([[antifungal]])<ref name=":0" />
* [[cannabidiol]]
* [[desipramine]] ([[tricyclic antidepressant]])<ref name=":0" />
* [[disulfiram]] ([[acetaldehyde dehydrogenase]] inhibitor)<ref name=":0" />
* [[entacapone]] ([[Catechol-O-methyl transferase|COMT]] inhibitor, used in [[Parkinson's disease]])<ref name=":0" />
* [[fenofibrate]] ([[fibrate]])<ref name=":0" />
* [[gabapentin]] ([[anticonvulsant]])
* [[grapefruit]] juice [[flavonoids]]
* [[isoniazid]] ([[Antibiotics|antibacterial]])<ref name=":0" /><ref name="pmid11868802">{{cite journal|year=2002|title=Isoniazid is a mechanism-based inhibitor of cytochrome P450 1A2, 2A6, 2C19 and 3A4 isoforms in human liver microsomes|journal=Eur. J. Clin. Pharmacol.|volume=57|issue=11|pages=799–804|doi=10.1007/s00228-001-0396-3|pmid=11868802|vauthors=Wen X, Wang JS, Neuvonen PJ, Backman JT}}</ref>
* [[ketoconazole]] ([[Antifungal medication|antifungal]])<ref name=":0" />
* [[letrozole]] ([[aromatase inhibitor]], used in [[breast cancer]])<ref name=":0" />
* [[methimazole]] ([[antithyroid agent]])<ref name=":0" />
* [[methoxsalen]] ([[furanocoumarin]], used in [[psoriasis]])<ref name=":0" />
* [[metyrapone]] (used to diagnose [[adrenal insufficiency]])<ref name=":0" />
* [[miconazole]] ([[antifungal]])<ref name=":0" />
* [[modafinil]] ([[wakefulness-promoting agent]])<ref name=":0" />
* [[nicotine]] ([[stimulant]])<ref name=":0" />
* [[orphenadrine]] ([[antihistamine]])<ref name=":0" />
* [[pilocarpine]] ([[muscarinic receptor]] agonist)<ref name=":0" />
* [[pregabalin]] ([[anticonvulsant]])
* [[selegiline]] ([[monoamine oxidase inhibitor]])<ref name=":0" /><ref name="pmid18065502">{{cite journal|year=2008|title=Selegiline is a mechanism-based inactivator of CYP2A6 inhibiting nicotine metabolism in humans and mice|journal=J. Pharmacol. Exp. Ther.|volume=324|issue=3|pages=992–9|doi=10.1124/jpet.107.133900|pmid=18065502|vauthors=Siu EC, Tyndale RF}}</ref>
* [[sulconazole]] ([[antifungal]])<ref name=":0" />
* [[tioconazole]] ([[antifungal]])<ref name=":0" />
* [[tranylcypromine]] ([[monoamine oxidase inhibitor]])<ref name=":0" />


||  
||  
* [[phenobarbital]] ([[anticonvulsant]])
* [[Barbiturate]]s
* [[rifampicin]] ([[bactericidal]])
** [[Amobarbital|amobarbita]]<nowiki/>l<ref name=":0" />
* [[dexamethazone]] ([[anti-inflammatory]] and [[immunosuppressant]])
** [[pentobarbital]]<ref name=":0" />
** [[phenobarbital]]<ref name=":0" />
** [[secobarbital]]<ref name=":0" />
* [[rifampicin]] ([[Antibiotics|antibacterial]])<ref name=":0" />
|-
|-
|}
|}
== See also ==
* [[List of cytochrome P450 modulators]]


==References==
==References==
{{reflist}}
{{reflist}}
==Further reading==
==Further reading==
{{refbegin | 2}}
{{refbegin | 2}}
* {{cite journal |author=Pelkonen O, Rautio A, Raunio H, Pasanen M |title=CYP2A6: a human coumarin 7-hydroxylase |journal=Toxicology |volume=144 |issue=1-3 |pages=139-47 |year=2000 |pmid=10781881}}
* {{cite journal |vauthors=Pelkonen O, Rautio A, Raunio H, Pasanen M |title=CYP2A6: a human coumarin 7-hydroxylase |journal=Toxicology |volume=144 |issue=1–3 |pages=139–47 |year=2000 |pmid=10781881 |doi=10.1016/S0300-483X(99)00200-0}}
{{PBB_Further_reading  
{{PBB_Further_reading  
| citations =  
| citations =  
*{{cite journal  | author=Fernandez-Salguero P, Gonzalez FJ |title=The CYP2A gene subfamily: species differences, regulation, catalytic activities and role in chemical carcinogenesis. |journal=Pharmacogenetics |volume=5 Spec No |issue=  |pages= S123-8 |year= 1995 |pmid= 7581481 |doi=  }}
*{{cite journal  | vauthors=Fernandez-Salguero P, Gonzalez FJ |title=The CYP2A gene subfamily: species differences, regulation, catalytic activities and role in chemical carcinogenesis   |journal=Pharmacogenetics |volume=5 |issue=  Special Issue|pages= S123–8 |year= 1995 |pmid= 7581481 |doi=10.1097/00008571-199512001-00013 }}
*{{cite journal  | author=Smith G, Stubbins MJ, Harries LW, Wolf CR |title=Molecular genetics of the human cytochrome P450 monooxygenase superfamily. |journal=Xenobiotica |volume=28 |issue= 12 |pages= 1129-65 |year= 1999 |pmid= 9890157 |doi=  }}
*{{cite journal  | vauthors=Smith G, Stubbins MJ, Harries LW, Wolf CR |title=Molecular genetics of the human cytochrome P450 monooxygenase superfamily |journal=Xenobiotica |volume=28 |issue= 12 |pages= 1129–65 |year= 1999 |pmid= 9890157 |doi=10.1080/004982598238868 }}
*{{cite journal  | author=Pelkonen O, Rautio A, Raunio H, Pasanen M |title=CYP2A6: a human coumarin 7-hydroxylase. |journal=Toxicology |volume=144 |issue= 1-3 |pages= 139-47 |year= 2000 |pmid= 10781881 |doi=  }}
*{{cite journal  | vauthors=Pelkonen O, Rautio A, Raunio H, Pasanen M |title=CYP2A6: a human coumarin 7-hydroxylase |journal=Toxicology |volume=144 |issue= 1–3 |pages= 139–47 |year= 2000 |pmid= 10781881 |doi=10.1016/S0300-483X(99)00200-0 }}
*{{cite journal  | author=Tyndale RF, Sellers EM |title=Genetic variation in CYP2A6-mediated nicotine metabolism alters smoking behavior. |journal=Therapeutic drug monitoring |volume=24 |issue= 1 |pages= 163-71 |year= 2002 |pmid= 11805739 |doi=  }}
*{{cite journal  | vauthors=Tyndale RF, Sellers EM |title=Genetic variation in CYP2A6-mediated nicotine metabolism alters smoking behavior |journal=Therapeutic drug monitoring |volume=24 |issue= 1 |pages= 163–71 |year= 2002 |pmid= 11805739 |doi=10.1097/00007691-200202000-00026 }}
*{{cite journal  | author=Xu C, Goodz S, Sellers EM, Tyndale RF |title=CYP2A6 genetic variation and potential consequences. |journal=Adv. Drug Deliv. Rev. |volume=54 |issue= 10 |pages= 1245-56 |year= 2003 |pmid= 12406643 |doi=  }}
*{{cite journal  | vauthors=Xu C, Goodz S, Sellers EM, Tyndale RF |title=CYP2A6 genetic variation and potential consequences |journal=Adv. Drug Deliv. Rev. |volume=54 |issue= 10 |pages= 1245–56 |year= 2003 |pmid= 12406643 |doi=10.1016/S0169-409X(02)00065-0 }}
*{{cite journal  | author=Kamataki T, Fujieda M, Kiyotani K, ''et al.'' |title=Genetic polymorphism of CYP2A6 as one of the potential determinants of tobacco-related cancer risk. |journal=Biochem. Biophys. Res. Commun. |volume=338 |issue= 1 |pages= 306-10 |year= 2005 |pmid= 16176798 |doi= 10.1016/j.bbrc.2005.08.268 }}
*{{cite journal  | vauthors=Kamataki T, Fujieda M, Kiyotani K |title=Genetic polymorphism of CYP2A6 as one of the potential determinants of tobacco-related cancer risk |journal=Biochem. Biophys. Res. Commun. |volume=338 |issue= 1 |pages= 306–10 |year= 2005 |pmid= 16176798 |doi= 10.1016/j.bbrc.2005.08.268 |display-authors=etal}}
*{{cite journal  | author=Maurice M, Emiliani S, Dalet-Beluche I, ''et al.'' |title=Isolation and characterization of a cytochrome P450 of the IIA subfamily from human liver microsomes. |journal=Eur. J. Biochem. |volume=200 |issue= 2 |pages= 511-7 |year= 1991 |pmid= 1889415 |doi=  }}
*{{cite journal  | vauthors=Maurice M, Emiliani S, Dalet-Beluche I |title=Isolation and characterization of a cytochrome P450 of the IIA subfamily from human liver microsomes |journal=Eur. J. Biochem. |volume=200 |issue= 2 |pages= 511–7 |year= 1991 |pmid= 1889415 |doi=10.1111/j.1432-1033.1991.tb16212.x |display-authors=etal}}
*{{cite journal  | author=Yun CH, Shimada T, Guengerich FP |title=Purification and characterization of human liver microsomal cytochrome P-450 2A6. |journal=Mol. Pharmacol. |volume=40 |issue= 5 |pages= 679-85 |year= 1991 |pmid= 1944238 |doi=  }}
*{{cite journal  | vauthors=Yun CH, Shimada T, Guengerich FP |title=Purification and characterization of human liver microsomal cytochrome P-450 2A6 |journal=Mol. Pharmacol. |volume=40 |issue= 5 |pages= 679–85 |year= 1991 |pmid= 1944238 |doi=  }}
*{{cite journal  | author=Yamano S, Tatsuno J, Gonzalez FJ |title=The CYP2A3 gene product catalyzes coumarin 7-hydroxylation in human liver microsomes. |journal=Biochemistry |volume=29 |issue= 5 |pages= 1322-9 |year= 1990 |pmid= 2322567 |doi=  }}
*{{cite journal  | vauthors=Yamano S, Tatsuno J, Gonzalez FJ |title=The CYP2A3 gene product catalyzes coumarin 7-hydroxylation in human liver microsomes |journal=Biochemistry |volume=29 |issue= 5 |pages= 1322–9 |year= 1990 |pmid= 2322567 |doi=10.1021/bi00457a031 }}
*{{cite journal  | author=Miles JS, Bickmore W, Brook JD, ''et al.'' |title=Close linkage of the human cytochrome P450IIA and P450IIB gene subfamilies: implications for the assignment of substrate specificity. |journal=Nucleic Acids Res. |volume=17 |issue= 8 |pages= 2907-17 |year= 1989 |pmid= 2726448 |doi=  }}
*{{cite journal  | vauthors=Miles JS, Bickmore W, Brook JD |title=Close linkage of the human cytochrome P450IIA and P450IIB gene subfamilies: implications for the assignment of substrate specificity |journal=Nucleic Acids Res. |volume=17 |issue= 8 |pages= 2907–17 |year= 1989 |pmid= 2726448 |doi=10.1093/nar/17.8.2907  | pmc=317701 |display-authors=etal}}
*{{cite journal  | author=Yamano S, Nagata K, Yamazoe Y, ''et al.'' |title=cDNA and deduced amino acid sequences of human P450 IIA3 (CYP2A3). |journal=Nucleic Acids Res. |volume=17 |issue= 12 |pages= 4888 |year= 1989 |pmid= 2748347 |doi=  }}
*{{cite journal  | vauthors=Yamano S, Nagata K, Yamazoe Y |title=cDNA and deduced amino acid sequences of human P450 IIA3 (CYP2A3) |journal=Nucleic Acids Res. |volume=17 |issue= 12 |pages= 4888 |year= 1989 |pmid= 2748347 |doi=10.1093/nar/17.12.4888 | pmc=318052  |display-authors=etal}}
*{{cite journal  | author=Phillips IR, Shephard EA, Ashworth A, Rabin BR |title=Isolation and sequence of a human cytochrome P-450 cDNA clone. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=82 |issue= 4 |pages= 983-7 |year= 1985 |pmid= 3856261 |doi=  }}
*{{cite journal  | vauthors=Phillips IR, Shephard EA, Ashworth A, Rabin BR |title=Isolation and sequence of a human cytochrome P-450 cDNA clone |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=82 |issue= 4 |pages= 983–7 |year= 1985 |pmid= 3856261 |doi=10.1073/pnas.82.4.983  | pmc=397177 }}
*{{cite journal  | author=Wainwright BJ, Watson EK, Shephard EA, Phillips IR |title=RFLP for a human cytochrome P-450 gene at 19q13.1-qter (HGM8 provisional designation CYPI). |journal=Nucleic Acids Res. |volume=13 |issue= 12 |pages= 4610 |year= 1985 |pmid= 4011450 |doi=  }}
*{{cite journal  | vauthors=Wainwright BJ, Watson EK, Shephard EA, Phillips IR |title=RFLP for a human cytochrome P-450 gene at 19q13.1-qter (HGM8 provisional designation CYPI) |journal=Nucleic Acids Res. |volume=13 |issue= 12 |pages= 4610 |year= 1985 |pmid= 4011450 |doi=10.1093/nar/13.12.4610  | pmc=321810 }}
*{{cite journal  | author=Fernandez-Salguero P, Hoffman SM, Cholerton S, ''et al.'' |title=A genetic polymorphism in coumarin 7-hydroxylation: sequence of the human CYP2A genes and identification of variant CYP2A6 alleles. |journal=Am. J. Hum. Genet. |volume=57 |issue= 3 |pages= 651-60 |year= 1995 |pmid= 7668294 |doi=  }}
*{{cite journal  | vauthors=Fernandez-Salguero P, Hoffman SM, Cholerton S |title=A genetic polymorphism in coumarin 7-hydroxylation: sequence of the human CYP2A genes and identification of variant CYP2A6 alleles |journal=Am. J. Hum. Genet. |volume=57 |issue= 3 |pages= 651–60 |year= 1995 |pmid= 7668294 |doi=  | pmc=1801261  |display-authors=etal}}
*{{cite journal  | author=Ding S, Lake BG, Friedberg T, Wolf CR |title=Expression and alternative splicing of the cytochrome P-450 CYP2A7. |journal=Biochem. J. |volume=306 ( Pt 1) |issue=  |pages= 161-6 |year= 1995 |pmid= 7864805 |doi=  }}
*{{cite journal  | vauthors=Ding S, Lake BG, Friedberg T, Wolf CR |title=Expression and alternative splicing of the cytochrome P-450 CYP2A7 | series=306 |journal=Biochem. J. |volume=( Pt 1) |issue=  |pages= 161–6 |year= 1995 |pmid= 7864805 |doi= | pmc=1136496 }}
*{{cite journal  | author=Hoffman SM, Fernandez-Salguero P, Gonzalez FJ, Mohrenweiser HW |title=Organization and evolution of the cytochrome P450 CYP2A-2B-2F subfamily gene cluster on human chromosome 19. |journal=J. Mol. Evol. |volume=41 |issue= 6 |pages= 894-900 |year= 1996 |pmid= 8587134 |doi=  }}
*{{cite journal  | vauthors=Hoffman SM, Fernandez-Salguero P, Gonzalez FJ, Mohrenweiser HW |title=Organization and evolution of the cytochrome P450 CYP2A-2B-2F subfamily gene cluster on human chromosome 19 |journal=J. Mol. Evol. |volume=41 |issue= 6 |pages= 894–900 |year= 1996 |pmid= 8587134 |doi=  10.1007/bf00173169}}
*{{cite journal  | author=Hadidi H, Zahlsen K, Idle JR, Cholerton S |title=A single amino acid substitution (Leu160His) in cytochrome P450 CYP2A6 causes switching from 7-hydroxylation to 3-hydroxylation of coumarin. |journal=Food Chem. Toxicol. |volume=35 |issue= 9 |pages= 903-7 |year= 1998 |pmid= 9409631 |doi=  }}
*{{cite journal  | vauthors=Hadidi H, Zahlsen K, Idle JR, Cholerton S |title=A single amino acid substitution (Leu160His) in cytochrome P450 CYP2A6 causes switching from 7-hydroxylation to 3-hydroxylation of coumarin |journal=Food Chem. Toxicol. |volume=35 |issue= 9 |pages= 903–7 |year= 1998 |pmid= 9409631 |doi= 10.1016/S0278-6915(97)00066-5 }}
*{{cite journal  | author=Oscarson M, Gullstén H, Rautio A, ''et al.'' |title=Genotyping of human cytochrome P450 2A6 (CYP2A6), a nicotine C-oxidase. |journal=FEBS Lett. |volume=438 |issue= 3 |pages= 201-5 |year= 1998 |pmid= 9827545 |doi=  }}
*{{cite journal  | vauthors=Oscarson M, Gullstén H, Rautio A |title=Genotyping of human cytochrome P450 2A6 (CYP2A6), a nicotine C-oxidase |journal=FEBS Lett. |volume=438 |issue= 3 |pages= 201–5 |year= 1998 |pmid= 9827545 |doi=10.1016/S0014-5793(98)01297-6 |display-authors=etal}}
}}
}}
{{refend}}
{{refend}}
==External links==
* {{UCSC gene info|CPA6}}
* {{UCSC gene info|CYP2A6}}


{{PDB Gallery|geneid=1548}}
{{Cytochrome P450}}
{{Cytochrome P450}}
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[[Category:Cytochrome P450]]
[[Category:Cytochrome P450]]
{{WH}}
{{WikiDoc Sources}}

Latest revision as of 10:15, 30 August 2017

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Cytochrome P450 2A6 (abbreviated CYP2A6) is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. CYP2A6 is the primary enzyme responsible for the oxidation of nicotine and cotinine. It is also involved in the metabolism of several pharmaceuticals, carcinogens, and a number of coumarin-type alkaloids. CYP2A6 is the only enzyme in the human body that appreciably catalyzes the 7-hydroxylation of coumarin, such that the formation of the product of this reaction, 7-hydroxycoumarin, is used as a probe for CYP2A6 activity.

The CYP2A6 gene is part of a large cluster of cytochrome P450 genes from the CYP2A, CYP2B and CYP2F subfamilies on chromosome 19q. The gene was formerly referred to as CYP2A3; however, it has been renamed CYP2A6.[1]

Interactive pathway map

Click on genes, proteins and metabolites below to link to respective articles.[§ 1]

[[File:
<imagemap> Image:FluoropyrimidineActivity_WP1601.png
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<imagemap> Image:FluoropyrimidineActivity_WP1601.png
|{{{bSize}}}px|alt=Fluorouracil (5-FU) Activity edit]]
Fluorouracil (5-FU) Activity edit
  1. ↑ The interactive pathway map can be edited at WikiPathways: "FluoropyrimidineActivity_WP1601".

Distribution

CYP2A6 localizes to the endoplasmic reticulum and is found predominantly in the liver.

Variability

Significant interindividual variability in CYP2A6 apoprotein and mRNA levels has been observed.

Induction

CYP2A6 is known to be inducible by phenobarbital and rifampicin, and it is suspected that other antiepileptic drugs may also have this effect.

CYP2A6 Ligands

Selected inducers, inhibitors and substrates of CYP2A6
Substrates Inhibitors Inducers

See also

References

  1. ↑ "Entrez Gene: CYP2A6 cytochrome P450, family 2, subfamily A, polypeptide 6".
  2. ↑ 2.00 2.01 2.02 2.03 2.04 2.05 2.06 2.07 2.08 2.09 2.10 2.11 2.12 2.13 2.14 2.15 2.16 2.17 2.18 2.19 2.20 2.21 2.22 2.23 2.24 2.25 2.26 2.27 2.28 2.29 Lacy CF, Armstrong LL, Goldman MP, Lance LL (2007). Cytochrome P450 Enzymes: Substrates, Inhibitors, and Inducers. Hudson, OH: LexiComp Inc. pp. 1899–1912.
  3. ↑ Wen X, Wang JS, Neuvonen PJ, Backman JT (2002). "Isoniazid is a mechanism-based inhibitor of cytochrome P450 1A2, 2A6, 2C19 and 3A4 isoforms in human liver microsomes". Eur. J. Clin. Pharmacol. 57 (11): 799–804. doi:10.1007/s00228-001-0396-3. PMID 11868802.
  4. ↑ Siu EC, Tyndale RF (2008). "Selegiline is a mechanism-based inactivator of CYP2A6 inhibiting nicotine metabolism in humans and mice". J. Pharmacol. Exp. Ther. 324 (3): 992–9. doi:10.1124/jpet.107.133900. PMID 18065502.

Further reading

External links

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