Biology:CYP2B6
![]() Generic protein structure example |
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]
References
- ↑ 1.0 1.1 1.2 1.3 Template:NCBI RefSeq
- ↑ 2.0 2.1 2.2 Center for Drug Evaluation and Research. "Drug Interactions & Labeling - Drug Development and Drug Interactions: Table of Substrates, Inhibitors and Inducers" (in en). https://www.fda.gov/Drugs/DevelopmentApprovalProcess/DevelopmentResources/DrugInteractionsLabeling/ucm093664.htm#classInhibit.
- ↑ 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 Swedish environmental classification of pharmaceuticals - FASS (drug catalog) - Facts for prescribers (Fakta för förskrivare). Retrieved July 2011
- ↑ 4.00 4.01 4.02 4.03 4.04 4.05 4.06 4.07 4.08 4.09 4.10 "Drug Interactions: Cytochrome P450 Drug Interaction Table". Indiana University School of Medicine. 2007. http://medicine.iupui.edu/flockhart/table.htm. 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
- ↑ "Role of Cytochrome P4502B6 Polymorphisms in Ketamine Metabolism and Clearance". Anesthesiology 125 (6): 1103–1112. December 2016. doi:10.1097/ALN.0000000000001392. PMID 27763887.
- ↑ "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. July 2013. doi:10.1007/s00216-013-7051-6. PMID 23774830.
- ↑ 8.0 8.1 8.2 8.3 8.4 8.5 "Evaluation of 227 drugs for in vitro inhibition of cytochrome P450 2B6". Journal of Clinical Pharmacology 46 (12): 1426–38. December 2006. doi:10.1177/0091270006293753. PMID 17101742.
- ↑ "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. February 2005. doi:10.1124/dmd.104.002428. PMID 15547048.
- ↑ "Molecular characterization of CYP2B6 substrates". Current Drug Metabolism 9 (5): 363–73. June 2008. doi:10.2174/138920008784746346. PMID 18537573.
- ↑ "Comparison of intravenous diltiazem and verapamil for the acute treatment of atrial fibrillation and atrial flutter". Pharmacotherapy 17 (6): 1238–45. 1997. doi:10.1002/j.1875-9114.1997.tb03087.x. PMID 9399606.
- ↑ "Orphenadrine and methimazole inhibit multiple cytochrome P450 enzymes in human liver microsomes". Drug Metabolism and Disposition 25 (3): 390–3. March 1997. PMID 9172960.
- ↑ Sridar, C.; Kenaan, C.; Hollenberg, P. F. (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. PMID 22936314.
- ↑ "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. August 2008. doi:10.1124/dmd.108.020552. PMID 18480186.
- ↑ "Inhibition of human recombinant cytochrome P450s by curcumin and curcumin decomposition products". Toxicology 235 (1–2): 83–91. June 2007. doi:10.1016/j.tox.2007.03.007. PMID 17433521.
- ↑ 16.0 16.1 16.2 16.3 16.4 "CYP2B6 mediates the in vitro hydroxylation of bupropion: potential drug interactions with other antidepressants". Drug Metabolism and Disposition 28 (10): 1176–83. October 2000. PMID 10997936.
- ↑ "Memantine: a treatment for Alzheimer's disease with a new formulation.". Aging Health 7 (3): 349–62. June 2011. doi:10.2217/ahe.11.31. http://www.medscape.com/viewarticle/748581_4.
Further reading
- "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. August 2010. doi:10.1186/1742-6405-7-32. PMID 20723261.
- "Induction of CYP2B6 and CYP3A4 expression by 1-aminobenzotriazole (ABT) in human hepatocytes". Drug Metabolism Letters 4 (3): 129–33. August 2010. doi:10.2174/187231210791698410. PMID 20642445.
- "Long-term efavirenz autoinduction and its effect on plasma exposure in HIV patients". Clinical Pharmacology and Therapeutics 88 (5): 676–84. November 2010. doi:10.1038/clpt.2010.172. PMID 20881953.
- "Molecular genetics of the human cytochrome P450 monooxygenase superfamily". Xenobiotica; the Fate of Foreign Compounds in Biological Systems 28 (12): 1129–65. December 1998. doi:10.1080/004982598238868. PMID 9890157.
- "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. December 2010. doi:10.1097/QAI.0b013e3181f52f0c. PMID 20861742.
- "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. December 2010. doi:10.1002/ajh.21889. PMID 21108329.
- "CYP2B6 gene single nucleotide polymorphisms and leukemia susceptibility". Annals of Hematology 90 (3): 293–9. March 2011. doi:10.1007/s00277-010-1085-z. PMID 20878158.
- "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. January 2004. doi:10.1097/00008571-200401000-00001. PMID 15128046.
- "Substrate specificity, regulation, and polymorphism of human cytochrome P450 2B6". Current Drug Metabolism 10 (7): 730–53. September 2009. doi:10.2174/138920009789895534. PMID 19702527.
- "The convergence of therapeutic drug monitoring and pharmacogenetic testing to optimize efavirenz therapy". Therapeutic Drug Monitoring 32 (5): 579–85. October 2010. doi:10.1097/FTD.0b013e3181f0634c. PMID 20720517.
- "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. September 2010. doi:10.1086/655470. PMID 20662624.
- "An approach based on a genome-wide association study reveals candidate loci for narcolepsy". Human Genetics 128 (4): 433–41. October 2010. doi:10.1007/s00439-010-0862-z. PMID 20677014.
- "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. December 2010. doi:10.1093/jac/dkq369. PMID 20952418.
- "Efavirenz plasma concentrations and cytochrome 2B6 polymorphisms". The Annals of Pharmacotherapy 44 (10): 1572–8. October 2010. doi:10.1345/aph.1P141. PMID 20841522.
- "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. January 2011. doi:10.1124/dmd.110.035246. PMID 20876786.
- "A large-scale candidate gene association study of age at menarche and age at natural menopause". Human Genetics 128 (5): 515–27. November 2010. doi:10.1007/s00439-010-0878-4. PMID 20734064.
- "Toward personalized medicine in renal transplantation". Transplantation Proceedings 42 (8): 2864–7. October 2010. doi:10.1016/j.transproceed.2010.08.009. PMID 20970553.
- "Influence of host genetic factors on efavirenz plasma and intracellular pharmacokinetics in HIV-1-infected patients". Pharmacogenomics 11 (9): 1223–34. September 2010. doi:10.2217/pgs.10.94. PMID 20860463.
- "Population pharmacokinetic-pharmacogenetic study of nevirapine in HIV-infected Cambodian patients". Antimicrobial Agents and Chemotherapy 54 (10): 4432–9. October 2010. doi:10.1128/AAC.00512-10. PMID 20696882. PMC 2944557. http://www.hal.inserm.fr/inserm-00517725/document.
- "OPRM1 and CYP2B6 gene variants as risk factors in methadone-related deaths". Clinical Pharmacology and Therapeutics 88 (3): 383–9. September 2010. doi:10.1038/clpt.2010.127. PMID 20668445.
External links
- CYP2B6 at the US 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.
![]() | Original source: https://en.wikipedia.org/wiki/CYP2B6.
Read more |