CYP2B6

Cytochrome P450, family 2, subfamily B, polypeptide 6
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 3IBD​, 3QOA​, 3QU8​, 3UA5​, 4I91​, 4RQL​, 4RRT​
Identifiers
Symbols	CYP2B6 ; CPB6; CYP2B; CYP2B7; CYP2B7P; CYPIIB6; EFVM; IIB1; P450
External IDs	OMIM: 123930 MGI: 88598 HomoloGene: 73894 IUPHAR: 1324 ChEMBL: 4729 GeneCards: CYP2B6 Gene
EC number	1.14.14.1
Gene ontology Molecular function • monooxygenase activity • iron ion binding • arachidonic acid epoxygenase activity • steroid hydroxylase activity • oxidoreductase activity, acting on paired donors, with incorporation or reduction of molecular oxygen, reduced flavin or flavoprotein as one donor, and incorporation of one atom of oxygen • oxygen binding • heme binding Cellular component • cytoplasm • endoplasmic reticulum membrane • intracellular membrane-bounded organelle Biological process • xenobiotic metabolic process • steroid metabolic process • drug metabolic process • epoxygenase P450 pathway • cellular ketone metabolic process • exogenous drug catabolic process • small molecule metabolic process • oxidation-reduction process Sources: Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	1555	13088
Ensembl	ENSG00000197408	ENSMUSG00000030483
UniProt	P20813	Q9WUD0
RefSeq (mRNA)	NM_000767	NM_009999
RefSeq (protein)	NP_000758	NP_034129
Location (UCSC)	Chr 19: 40.99 – 41.02 Mb	Chr 7: 25.9 – 25.93 Mb
PubMed search

Cytochrome P450 2B6 is an enzyme that in humans is encoded by the CYP2B6 gene.^[1] CYP2B6 is a member of the Cytochrome P450 group of enzymes. Along with CYP2A6, it is involved with metabolizing nicotine, along with many other substances.^[1]

Function

This gene, CYP2B6, encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the endoplasmic reticulum and its expression is induced by phenobarbital. The enzyme is known to metabolize some xenobiotics, such as the anti-cancer drugs cyclophosphamide and ifosphamide.^[1]

Gene

Transcript variants for this gene have been described; however, it has not been resolved whether these transcripts are in fact produced by this gene or by a closely related pseudogene, CYP2B7. Both the gene and the pseudogene are located in the middle of a CYP2A pseudogene found in a large cluster of cytochrome P450 genes from the CYP2A, CYP2B and CYP2F subfamilies on chromosome 19q.^[1]

CYP2B6 Ligands

Following is a table of selected substrates, inducers and inhibitors of CYP2B6.

Inhibitors of CYP2B6 can be classified by their potency, such as:

• Strong inhibitor being one that causes at least a 5-fold increase in the plasma AUC values, or more than 80% decrease in clearance.^[2]
• Moderate inhibitor being one that causes at least a 2-fold increase in the plasma AUC values, or 50-80% decrease in clearance.^[2]
• Weak inhibitor being one that causes at least a 1.25-fold but less than 2-fold increase in the plasma AUC values, or 20-50% decrease in clearance.^[2]

Substrates	Inhibitors	Inducers
alfentanil[3] (opioid analgesic) bupropion[2][3] (antidepressant) cyclophosphamide[2][3] (Alkylating antineoplastic agent) efavirenz[2][3] (NNRTI) ifosfamide[2][3] (Alkylating antineoplastic agent) methadone[2] (opiate replacement therapy) nevirapine[3] (NNRTI) propofol[3] (anesthetic) sertraline[4] sorafenib[2] (protein kinase inhibitor) tamoxifen[3] (SERM) valproic acid[3] (anticonvulsant) methoxetamine[5]	Strong: orphenadrine[3][6] (first-generation antihistamine) Unspecified potency ticlopidine[2] (antiplatelet) ThioTEPA[2] (anticancer) Curcumin[7] (constituent of turmeric)	rifampicin[2][3] (bactericidal) carbamazepine[3] (anticonvulsant, mood stabilizer) phenobarbital[2] (anticonvulsant ) phenytoin[2] (antiepileptic)

References

1. "Entrez Gene: cytochrome P450".
2. Flockhart DA (2007). "Drug Interactions: Cytochrome P₄₅₀ Drug Interaction Table". Indiana University School of Medicine. Retrieved on December 25, 2008.
3. Swedish environmental classification of pharmaceuticals - FASS (drug catalog) - Facts for prescribers (Fakta för förskrivare). Retrieved July 2011
4. Obach RS, Cox LM, Tremaine LM (2005). "Sertraline is metabolized by multiple cytochrome P450 enzymes, monoamine oxidases, and glucuronyl transferases in human: an in vitro study". Drug Metab. Dispos. 33 (2): 262–70. doi:10.1124/dmd.104.002428. PMID 15547048.
5. Meyer MR, Bach M, Welter J, Bovens M, Turcant A, Maurer HH (2013). "Ketamine-derived designer drug methoxetamine: metabolism including isoenzyme kinetics and toxicological detectability using GC-MS and LC-(HR-)MSn". Anal Bioanal Chem 405 (19): 6307–21. doi:10.1007/s00216-013-7051-6. PMID 23774830.
6. Guo Z, Raeissi S, White RB, Stevens JC (1997). "Orphenadrine and methimazole inhibit multiple cytochrome P450 enzymes in human liver microsomes". Drug Metab. Dispos. 25 (3): 390–3. PMID 9172960.
7. Volak LP, Ghirmai S, Cashman JR, Court MH (August 2008). "Curcuminoids inhibit multiple human cytochromes P450, UDP-glucuronosyltransferase, and sulfotransferase enzymes, whereas piperine is a relatively selective CYP3A4 inhibitor". Drug Metab. Dispos. 36 (8): 1594–605. doi:10.1124/dmd.108.020552. PMC 2574793. PMID 18480186.

Further reading

• Gounden V, van Niekerk C, Snyman T, George JA (2010). "Presence of the CYP2B6 516G> T polymorphism, increased plasma Efavirenz concentrations and early neuropsychiatric side effects in South African HIV-infected patients.". AIDS Res Ther 7: 32. doi:10.1186/1742-6405-7-32. PMC 2933581. PMID 20723261.
• Yang K, Koh KH, Jeong H (2010). "Induction of CYP2B6 and CYP3A4 expression by 1-aminobenzotriazole (ABT) in human hepatocytes". Drug Metab Lett 4 (3): 129–33. doi:10.2174/187231210791698410. PMID 20642445.
• Ngaimisi E, Mugusi S, Minzi OM; et al. (2010). "Long-term efavirenz autoinduction and its effect on plasma exposure in HIV patients". Clin. Pharmacol. Ther. 88 (5): 676–84. doi:10.1038/clpt.2010.172. PMID 20881953.
• Smith G, Stubbins MJ, Harries LW, Wolf CR (1998). "Molecular genetics of the human cytochrome P450 monooxygenase superfamily". Xenobiotica 28 (12): 1129–65. doi:10.1080/004982598238868. PMID 9890157.
• Svärd J, Spiers JP, Mulcahy F, Hennessy M (2010). "Nuclear Receptor-Mediated Induction of CYP450 by Antiretrovirals: Functional Consequences of NR1I2 (PXR) Polymorphisms and Differential Prevalence in Whites and Sub-Saharan Africans". J. Acquir. Immune Defic. Syndr. 55 (5): HASH(0x271b490). doi:10.1097/QAI.0b013e3181f52f0c. PMID 20861742.
• Melanson SE, Stevenson K, Kim H; et al. (2010). "Allelic variations in CYP2B6 and CYP2C19 and survival of patients receiving cyclophosphamide prior to myeloablative hematopoietic stem cell transplantation". Am. J. Hematol. 85 (12): 967–71. doi:10.1002/ajh.21889. PMID 21108329.
• Yuan ZH, Liu Q, Zhang Y; et al. (2010). "CYP2B6 gene single nucleotide polymorphisms and leukemia susceptibility". Ann. Hematol. 90 (3): HASH(0x2bd3fb0). doi:10.1007/s00277-010-1085-z. PMID 20878158.
• Nelson DR, Zeldin DC, Hoffman SM; et al. (2004). "Comparison of cytochrome P450 (CYP) genes from the mouse and human genomes, including nomenclature recommendations for genes, pseudogenes and alternative-splice variants". Pharmacogenetics 14 (1): 1–18. doi:10.1097/00008571-200401000-00001. PMID 15128046.
• Mo SL, Liu YH, Duan W; et al. (2009). "Substrate specificity, regulation, and polymorphism of human cytochrome P450 2B6". Curr. Drug Metab. 10 (7): 730–53. doi:10.2174/138920009789895534. PMID 19702527.
• Figueroa SC, de Gatta MF, GarcÃa LH; et al. (2010). "The convergence of therapeutic drug monitoring and pharmacogenetic testing to optimize efavirenz therapy". Ther Drug Monit 32 (5): 579–85. doi:10.1097/FTD.0b013e3181f0634c. PMID 20720517.
• Ribaudo HJ, Liu H, Schwab M; et al. (2010). "Effect of CYP2B6, ABCB1, and CYP3A5 polymorphisms on efavirenz pharmacokinetics and treatment response: an AIDS Clinical Trials Group study". J. Infect. Dis. 202 (5): 717–22. doi:10.1086/655470. PMC 2919241. PMID 20662624.
• Shimada M, Miyagawa T, Kawashima M; et al. (2010). "An approach based on a genome-wide association study reveals candidate loci for narcolepsy". Hum. Genet. 128 (4): 433–41. doi:10.1007/s00439-010-0862-z. PMID 20677014.
• Jamshidi Y, Moreton M, McKeown DA; et al. (2010). "Tribal ethnicity and CYP2B6 genetics in Ugandan and Zimbabwean populations in the UK: implications for efavirenz dosing in HIV infection". J. Antimicrob. Chemother. 65 (12): 2614–9. doi:10.1093/jac/dkq369. PMID 20952418.
• Lindfelt T, O'Brien J, Song JC; et al. (2010). "Efavirenz plasma concentrations and cytochrome 2B6 polymorphisms". Ann Pharmacother 44 (10): 1572–8. doi:10.1345/aph.1P141. PMID 20841522.
• Chung JY, Cho JY, Lim HS; et al. (2011). "Effects of pregnane X receptor (NR1I2) and CYP2B6 genetic polymorphisms on the induction of bupropion hydroxylation by rifampin". Drug Metab. Dispos. 39 (1): 92–7. doi:10.1124/dmd.110.035246. PMID 20876786.
• He C, Kraft P, Chasman DI; et al. (2010). "A large-scale candidate gene association study of age at menarche and age at natural menopause". Hum. Genet. 128 (5): 515–27. doi:10.1007/s00439-010-0878-4. PMC 2967297. PMID 20734064.
• Lampreabe I, Gainza de los Rios FJ, Arrieta Gutiérrez A; et al. (2010). "Toward personalized medicine in renal transplantation". Transplant. Proc. 42 (8): 2864–7. doi:10.1016/j.transproceed.2010.08.009. PMID 20970553.
• Elens L, Vandercam B, Yombi JC; et al. (2010). "Influence of host genetic factors on efavirenz plasma and intracellular pharmacokinetics in HIV-1-infected patients". Pharmacogenomics 11 (9): 1223–34. doi:10.2217/pgs.10.94. PMID 20860463.
• Chou M, Bertrand J, Segeral O; et al. (2010). "Population pharmacokinetic-pharmacogenetic study of nevirapine in HIV-infected Cambodian patients". Antimicrob. Agents Chemother. 54 (10): 4432–9. doi:10.1128/AAC.00512-10. PMC 2944557. PMID 20696882.
• Bunten H, Liang WJ, Pounder DJ; et al. (2010). "OPRM1 and CYP2B6 gene variants as risk factors in methadone-related deaths". Clin. Pharmacol. Ther. 88 (3): 383–9. doi:10.1038/clpt.2010.127. PMID 20668445.

External links

• CYP2B6 at the US National Library of Medicine Medical Subject Headings (MeSH)

This article incorporates text from the United States National Library of Medicine, which is in the public domain.