Biology:CYP2B6

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
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]
Substrates Inhibitors Inducers
Strong:

Moderate:

Unspecified potency

References

  1. ↑ 1.0 1.1 1.2 1.3 Template:NCBI RefSeq
  2. ↑ 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. ↑ 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. ↑ 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.
  5. ↑ 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
  6. ↑ "Role of Cytochrome P4502B6 Polymorphisms in Ketamine Metabolism and Clearance". Anesthesiology 125 (6): 1103–1112. December 2016. doi:10.1097/ALN.0000000000001392. PMID 27763887. 
  7. ↑ "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. ↑ 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. 
  9. ↑ "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. 
  10. ↑ "Molecular characterization of CYP2B6 substrates". Current Drug Metabolism 9 (5): 363–73. June 2008. doi:10.2174/138920008784746346. PMID 18537573. 
  11. ↑ "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. 
  12. ↑ "Orphenadrine and methimazole inhibit multiple cytochrome P450 enzymes in human liver microsomes". Drug Metabolism and Disposition 25 (3): 390–3. March 1997. PMID 9172960. 
  13. ↑ 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. 
  14. ↑ "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. 
  15. ↑ "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. ↑ 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. 
  17. ↑ "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

External links

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



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