CYP2B6
| CYP2B6 | |||||||||||||||||||||||||||||||||||||||||||||||||||
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| Aliases | CYP2B6, CPB6, CYP2B, CYP2B7, CYP2B7P, CYPIIB6, EFVM, IIB1, P450, cytochrome P450 family 2 subfamily B member 6, Cytochrome P450 2B6 | ||||||||||||||||||||||||||||||||||||||||||||||||||
| External IDs | OMIM: 123930; MGI: 88598; HomoloGene: 73894; GeneCards: CYP2B6; OMA:CYP2B6 - orthologs | ||||||||||||||||||||||||||||||||||||||||||||||||||
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Cytochrome P450 2B6 is an enzyme that in humans is encoded by the CYP2B6 gene.[5] 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.[5]
Function
[edit]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.[5]
Gene
[edit]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.[5]
CYP2B6 ligands
[edit]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.[6]
- Moderate inhibitor being one that causes at least a 2-fold increase in the plasma AUC values, or 50-80% decrease in clearance.[6]
- 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.[6]
References
[edit]- ^ a b c GRCh38: Ensembl release 89: ENSG00000197408 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030483 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ a b c d
This article incorporates public domain material from "Entrez Gene: cytochrome P450". Reference Sequence collection. National Center for Biotechnology Information.
- ^ a b c Center for Drug Evaluation and Research. "Drug Interactions & Labeling - Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers". www.fda.gov. Retrieved 2016-06-01.
- ^ a b c d e f g h i j k l m Swedish environmental classification of pharmaceuticals - FASS (drug catalog) - Facts for prescribers (Fakta för förskrivare). Retrieved July 2011
- ^ a b c d e f g h i j k Flockhart DA (2007). "Drug Interactions: Cytochrome P450 Drug Interaction Table". Indiana University School of Medicine. Archived from the original on 2007-10-10. Retrieved 2011-07-10. Retrieved on December 25, 2008.
- ^ Alkattan, A., & Alsalameen, E. (2021). Polymorphisms of genes related to phase-I metabolic enzymes affecting the clinical efficacy and safety of clopidogrel treatment. Expert opinion on drug metabolism & toxicology, 10.1080/17425255.2021.1925249. Advance online publication. https://doi.org/10.1080/17425255.2021.1925249
- ^ Rao LK, Flaker AM, Friedel CC, Kharasch ED (December 2016). "Role of Cytochrome P4502B6 Polymorphisms in Ketamine Metabolism and Clearance". Anesthesiology. 125 (6): 1103–1112. doi:10.1097/ALN.0000000000001392. PMID 27763887. S2CID 41380105.
- ^ Meyer MR, Bach M, Welter J, Bovens M, Turcant A, Maurer HH (July 2013). "Ketamine-derived designer drug methoxetamine: metabolism including isoenzyme kinetics and toxicological detectability using GC-MS and LC-(HR-)MSn". Analytical and Bioanalytical Chemistry. 405 (19): 6307–21. doi:10.1007/s00216-013-7051-6. PMID 23774830. S2CID 27966043.
- ^ a b c d e f Walsky RL, Astuccio AV, Obach RS (December 2006). "Evaluation of 227 drugs for in vitro inhibition of cytochrome P450 2B6". Journal of Clinical Pharmacology. 46 (12): 1426–38. doi:10.1177/0091270006293753. PMID 17101742. S2CID 40915941.
- ^ Obach RS, Cox LM, Tremaine LM (February 2005). "Sertraline is metabolized by multiple cytochrome P450 enzymes, monoamine oxidases, and glucuronyl transferases in human: an in vitro study". Drug Metabolism and Disposition. 33 (2): 262–70. doi:10.1124/dmd.104.002428. PMID 15547048. S2CID 7254643.
- ^ Ekins S, Iyer M, Krasowski MD, Kharasch ED (June 2008). "Molecular characterization of CYP2B6 substrates". Current Drug Metabolism. 9 (5): 363–73. doi:10.2174/138920008784746346. PMC 2426921. PMID 18537573.
- ^ Phillips BG, Gandhi AJ, Sanoski CA, Just VL, Bauman JL (1997). "Comparison of intravenous diltiazem and verapamil for the acute treatment of atrial fibrillation and atrial flutter". Pharmacotherapy. 17 (6): 1238–45. doi:10.1002/j.1875-9114.1997.tb03087.x. PMID 9399606. S2CID 20269145.
- ^ Guo Z, Raeissi S, White RB, Stevens JC (March 1997). "Orphenadrine and methimazole inhibit multiple cytochrome P450 enzymes in human liver microsomes". Drug Metabolism and Disposition. 25 (3): 390–3. PMID 9172960.
- ^ Kondža M, Mandić M, Ivančić I, Vladimir-Knežević S, Brizić I (2023-01-16). "Artemisia annua L. Extracts Irreversibly Inhibit the Activity of CYP2B6 and CYP3A4 Enzymes". Biomedicines. 11 (1): 232. doi:10.3390/biomedicines11010232. ISSN 2227-9059. PMC 9855681. PMID 36672740.
- ^ Sridar C, Kenaan C, Hollenberg PF (2012). "Inhibition of Bupropion Metabolism by Selegiline: Mechanism-Based Inactivation of Human CYP2B6 and Characterization of Glutathione and Peptide Adducts". Drug Metabolism and Disposition: The Biological Fate of Chemicals. 40 (12): 2256–2266. doi:10.1124/dmd.112.046979. PMC 3500550. PMID 22936314.
- ^ 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 Metabolism and Disposition. 36 (8): 1594–605. doi:10.1124/dmd.108.020552. PMC 2574793. PMID 18480186.
- ^ Appiah-Opong R, Commandeur JN, van Vugt-Lussenburg B, Vermeulen NP (June 2007). "Inhibition of human recombinant cytochrome P450s by curcumin and curcumin decomposition products". Toxicology. 235 (1–2): 83–91. Bibcode:2007Toxgy.235...83A. doi:10.1016/j.tox.2007.03.007. PMID 17433521.
- ^ a b c d e Hesse LM, Venkatakrishnan K, Court MH, von Moltke LL, Duan SX, Shader RI, Greenblatt DJ (October 2000). "CYP2B6 mediates the in vitro hydroxylation of bupropion: potential drug interactions with other antidepressants". Drug Metabolism and Disposition. 28 (10): 1176–83. PMID 10997936.
- ^ Makino KM, Porsteinsson AP (June 2011). "Memantine: a treatment for Alzheimer's disease with a new formulation". Aging Health. 7 (3): 349–62. doi:10.2217/ahe.11.31.
Further reading
[edit]- Gounden V, van Niekerk C, Snyman T, George JA (August 2010). "Presence of the CYP2B6 516G> T polymorphism, increased plasma Efavirenz concentrations and early neuropsychiatric side effects in South African HIV-infected patients". AIDS Research and Therapy. 7: 32. doi:10.1186/1742-6405-7-32. PMC 2933581. PMID 20723261.
- Yang K, Koh KH, Jeong H (August 2010). "Induction of CYP2B6 and CYP3A4 expression by 1-aminobenzotriazole (ABT) in human hepatocytes". Drug Metabolism Letters. 4 (3): 129–33. doi:10.2174/187231210791698410. PMC 3697095. PMID 20642445.
- Ngaimisi E, Mugusi S, Minzi OM, Sasi P, Riedel KD, Suda A, Ueda N, Janabi M, Mugusi F, Haefeli WE, Burhenne J, Aklillu E (November 2010). "Long-term efavirenz autoinduction and its effect on plasma exposure in HIV patients". Clinical Pharmacology and Therapeutics. 88 (5): 676–84. doi:10.1038/clpt.2010.172. PMID 20881953. S2CID 24749169.
- Smith G, Stubbins MJ, Harries LW, Wolf CR (December 1998). "Molecular genetics of the human cytochrome P450 monooxygenase superfamily". Xenobiotica; the Fate of Foreign Compounds in Biological Systems. 28 (12): 1129–65. doi:10.1080/004982598238868. PMID 9890157.
- Svärd J, Spiers JP, Mulcahy F, Hennessy M (December 2010). "Nuclear receptor-mediated induction of CYP450 by antiretrovirals: functional consequences of NR1I2 (PXR) polymorphisms and differential prevalence in whites and sub-Saharan Africans". Journal of Acquired Immune Deficiency Syndromes. 55 (5): 536–49. doi:10.1097/QAI.0b013e3181f52f0c. PMID 20861742. S2CID 205996665.
- Melanson SE, Stevenson K, Kim H, Antin JH, Court MH, Ho VT, Ritz J, Soiffer RJ, Kuo FC, Longtine JA, Jarolim P (December 2010). "Allelic variations in CYP2B6 and CYP2C19 and survival of patients receiving cyclophosphamide prior to myeloablative hematopoietic stem cell transplantation". American Journal of Hematology. 85 (12): 967–71. doi:10.1002/ajh.21889. PMID 21108329. S2CID 25737167.
- Yuan ZH, Liu Q, Zhang Y, Liu HX, Zhao J, Zhu P (March 2011). "CYP2B6 gene single nucleotide polymorphisms and leukemia susceptibility". Annals of Hematology. 90 (3): 293–9. doi:10.1007/s00277-010-1085-z. PMID 20878158. S2CID 19318796.
- Nelson DR, Zeldin DC, Hoffman SM, Maltais LJ, Wain HM, Nebert DW (January 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, Wei MQ, Kanwar JR, Zhou SF (September 2009). "Substrate specificity, regulation, and polymorphism of human cytochrome P450 2B6". Current Drug Metabolism. 10 (7): 730–53. doi:10.2174/138920009789895534. PMID 19702527.
- Cabrera Figueroa S, Fernández de Gatta M, Hernández García L, Domínguez-Gil Hurlé A, Bustos Bernal C, Sepúlveda Correa R, García Sánchez MJ (October 2010). "The convergence of therapeutic drug monitoring and pharmacogenetic testing to optimize efavirenz therapy". Therapeutic Drug Monitoring. 32 (5): 579–85. doi:10.1097/FTD.0b013e3181f0634c. PMID 20720517. S2CID 24793535.
- Ribaudo HJ, Liu H, Schwab M, Schaeffeler E, Eichelbaum M, Motsinger-Reif AA, Ritchie MD, Zanger UM, Acosta EP, Morse GD, Gulick RM, Robbins GK, Clifford D, Haas DW (September 2010). "Effect of CYP2B6, ABCB1, and CYP3A5 polymorphisms on efavirenz pharmacokinetics and treatment response: an AIDS Clinical Trials Group study". The Journal of Infectious Diseases. 202 (5): 717–22. doi:10.1086/655470. PMC 2919241. PMID 20662624.
- Shimada M, Miyagawa T, Kawashima M, Tanaka S, Honda Y, Honda M, Tokunaga K (October 2010). "An approach based on a genome-wide association study reveals candidate loci for narcolepsy". Human Genetics. 128 (4): 433–41. doi:10.1007/s00439-010-0862-z. PMID 20677014. S2CID 24207887.
- Jamshidi Y, Moreton M, McKeown DA, Andrews S, Nithiyananthan T, Tinworth L, Holt DW, Sadiq ST (December 2010). "Tribal ethnicity and CYP2B6 genetics in Ugandan and Zimbabwean populations in the UK: implications for efavirenz dosing in HIV infection". The Journal of Antimicrobial Chemotherapy. 65 (12): 2614–9. doi:10.1093/jac/dkq369. PMID 20952418.
- Lindfelt T, O'Brien J, Song JC, Patel R, Winslow DL (October 2010). "Efavirenz plasma concentrations and cytochrome 2B6 polymorphisms". The Annals of Pharmacotherapy. 44 (10): 1572–8. doi:10.1345/aph.1P141. PMID 20841522. S2CID 24188775.
- Chung JY, Cho JY, Lim HS, Kim JR, Yu KS, Lim KS, Shin SG, Jang IJ (January 2011). "Effects of pregnane X receptor (NR1I2) and CYP2B6 genetic polymorphisms on the induction of bupropion hydroxylation by rifampin". Drug Metabolism and Disposition. 39 (1): 92–7. doi:10.1124/dmd.110.035246. PMID 20876786. S2CID 15380723.
- He C, Kraft P, Chasman DI, Buring JE, Chen C, Hankinson SE, Paré G, Chanock S, Ridker PM, Hunter DJ (November 2010). "A large-scale candidate gene association study of age at menarche and age at natural menopause". Human Genetics. 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, Jofre-Monseny L, Rodriguez M, Amenabar Iribar JJ, Zárraga Larrondo S, Tejedor D, Martinez A, Olano-Martin E (October 2010). "Toward personalized medicine in renal transplantation". Transplantation Proceedings. 42 (8): 2864–7. doi:10.1016/j.transproceed.2010.08.009. PMID 20970553.
- Elens L, Vandercam B, Yombi JC, Lison D, Wallemacq P, Haufroid V (September 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, Verstuyft C, Borand L, Comets E, Le Tiec C, Becquemont L, Ouk V, Mentre F, Taburet AM (October 2010). "Population pharmacokinetic-pharmacogenetic study of nevirapine in HIV-infected Cambodian patients". Antimicrobial Agents and Chemotherapy. 54 (10): 4432–9. doi:10.1128/AAC.00512-10. PMC 2944557. PMID 20696882.
- Bunten H, Liang WJ, Pounder DJ, Seneviratne C, Osselton D (September 2010). "OPRM1 and CYP2B6 gene variants as risk factors in methadone-related deaths". Clinical Pharmacology and Therapeutics. 88 (3): 383–9. doi:10.1038/clpt.2010.127. PMID 20668445. S2CID 28983025.
External links
[edit]- CYP2B6 at the U.S. National Library of Medicine Medical Subject Headings (MeSH)
- Human CYP2B6 genome location and CYP2B6 gene details page in the UCSC Genome Browser.
- Overview of all the structural information available in the PDB for UniProt: P20813 (Cytochrome P450 2B6) at the PDBe-KB.
This article incorporates text from the United States National Library of Medicine, which is in the public domain.
