CYP2B6

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]

CYP2B6
Available structures
PDBOrtholog search: PDBe RCSB
Identifiers
AliasesCYP2B6, CPB6, CYP2B, CYP2B7, CYP2B7P, CYPIIB6, EFVM, IIB1, P450, cytochrome P450 family 2 subfamily B member 6, Cytochrome P450 2B6
External IDsOMIM: 123930 MGI: 88598 HomoloGene: 73894 GeneCards: CYP2B6
Orthologs
SpeciesHumanMouse
Entrez

1555

13088

Ensembl

ENSG00000197408

ENSMUSG00000030483

UniProt

P20813

P12791

RefSeq (mRNA)

NM_000767

NM_009999

RefSeq (protein)

NP_000758

n/a

Location (UCSC)Chr 19: 40.99 – 41.02 MbChr 7: 25.6 – 25.63 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

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.[5]

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.[5]

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.[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]
SubstratesInhibitorsInducers
Strong:

Moderate:

Unspecified potency

References
  1. GRCh38: Ensembl release 89: ENSG00000197408 - Ensembl, May 2017
  2. GRCm38: Ensembl release 89: ENSMUSG00000030483 - Ensembl, May 2017
  3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. "Entrez Gene: cytochrome P450".
  6. 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.
  7. Swedish environmental classification of pharmaceuticals - FASS (drug catalog) - Facts for prescribers (Fakta för förskrivare). Retrieved July 2011
  8. Flockhart DA (2007). "Drug Interactions: Cytochrome P450 Drug Interaction Table". Indiana University School of Medicine. Retrieved on December 25, 2008.
  9. 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
  10. 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.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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. PMID 9399606.
  16. 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.
  17. 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. PMC 3500550. PMID 22936314.
  18. 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.
  19. 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. doi:10.1016/j.tox.2007.03.007. PMID 17433521.
  20. 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.
  21. 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
  • 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.

This article is issued from Wikipedia. The text is licensed under Creative Commons - Attribution - Sharealike. Additional terms may apply for the media files.