CYP2B6

Last updated
CYP2B6
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
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
Orthologs
SpeciesHumanMouse
Entrez
Ensembl
UniProt
RefSeq (mRNA)

NM_000767

NM_009999

RefSeq (protein)

NP_000758

n/a

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

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]

Contents

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:

SubstratesInhibitorsInducers
Strong:

Moderate:

Unspecified potency

Related Research Articles

<span class="mw-page-title-main">Cytochrome P450</span> Class of enzymes

Cytochromes P450 are a superfamily of enzymes containing heme as a cofactor that mostly, but not exclusively, function as monooxygenases. In mammals, these proteins oxidize steroids, fatty acids, and xenobiotics, and are important for the clearance of various compounds, as well as for hormone synthesis and breakdown, steroid hormone synthesis, drug metabolism, and the biosynthesis of defensive compounds, fatty acids, and hormones. CYP450 enzymes convert xenobiotics into hydrophilic derivatives, which are more readily excreted. In almost all of the transformations that they catalyze, P450's affect hydroxylation.

<span class="mw-page-title-main">CYP3A4</span> Enzyme that metabolizes substances by oxidation

Cytochrome P450 3A4 is an important enzyme in the body, mainly found in the liver and in the intestine, which in humans is encoded by CYP3A4 gene. It oxidizes small foreign organic molecules (xenobiotics), such as toxins or drugs, so that they can be removed from the body. It is highly homologous to CYP3A5, another important CYP3A enzyme.

<span class="mw-page-title-main">CYP2D6</span> Human liver enzyme

Cytochrome P450 2D6 (CYP2D6) is an enzyme that in humans is encoded by the CYP2D6 gene. CYP2D6 is primarily expressed in the liver. It is also highly expressed in areas of the central nervous system, including the substantia nigra.

<span class="mw-page-title-main">CYP2E1</span> Protein-coding gene in the species Homo sapiens

Cytochrome P450 2E1 is a member of the cytochrome P450 mixed-function oxidase system, which is involved in the metabolism of xenobiotics in the body. This class of enzymes is divided up into a number of subcategories, including CYP1, CYP2, and CYP3, which as a group are largely responsible for the breakdown of foreign compounds in mammals.

<span class="mw-page-title-main">CYP1A2</span> Enzyme in the human body

Cytochrome P450 1A2, a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the human body. In humans, the CYP1A2 enzyme is encoded by the CYP1A2 gene.

<span class="mw-page-title-main">Grapefruit–drug interactions</span> Drug interactions with grapefruit juice

Some fruit juices and fruits can interact with numerous drugs, in many cases causing adverse effects. The effect is most studied with grapefruit and grapefruit juice, but similar effects have been observed with certain other citrus fruits.

<span class="mw-page-title-main">CYP2C9</span> Enzyme protein

Cytochrome P450 family 2 subfamily C member 9 is an enzyme protein. The enzyme is involved in the metabolism, by oxidation, of both xenobiotics, including drugs, and endogenous compounds, including fatty acids. In humans, the protein is encoded by the CYP2C9 gene. The gene is highly polymorphic, which affects the efficiency of the metabolism by the enzyme.

<span class="mw-page-title-main">CYP2C19</span> Mammalian protein found in humans

Cytochrome P450 2C19 is an enzyme protein. It is a member of the CYP2C subfamily of the cytochrome P450 mixed-function oxidase system. This subfamily includes enzymes that catalyze metabolism of xenobiotics, including some proton pump inhibitors and antiepileptic drugs. In humans, it is the CYP2C19 gene that encodes the CYP2C19 protein. CYP2C19 is a liver enzyme that acts on at least 10% of drugs in current clinical use, most notably the antiplatelet treatment clopidogrel (Plavix), drugs that treat pain associated with ulcers, such as omeprazole, antiseizure drugs such as mephenytoin, the antimalarial proguanil, and the anxiolytic diazepam.

<span class="mw-page-title-main">CYP1A1</span> Protein-coding gene in the species Homo sapiens

Cytochrome P450, family 1, subfamily A, polypeptide 1 is a protein that in humans is encoded by the CYP1A1 gene. The protein is a member of the cytochrome P450 superfamily of enzymes.

<span class="mw-page-title-main">Cholesterol 7 alpha-hydroxylase</span> Protein-coding gene in the species Homo sapiens

Cholesterol 7 alpha-hydroxylase also known as cholesterol 7-alpha-monooxygenase or cytochrome P450 7A1 (CYP7A1) is an enzyme that in humans is encoded by the CYP7A1 gene which has an important role in cholesterol metabolism. It is a cytochrome P450 enzyme, which belongs to the oxidoreductase class, and converts cholesterol to 7-alpha-hydroxycholesterol, the first and rate limiting step in bile acid synthesis.

<span class="mw-page-title-main">UGT2B7</span> Protein-coding gene in the species Homo sapiens

UGT2B7 (UDP-Glucuronosyltransferase-2B7) is a phase II metabolism isoenzyme found to be active in the liver, kidneys, epithelial cells of the lower gastrointestinal tract and also has been reported in the brain. In humans, UDP-Glucuronosyltransferase-2B7 is encoded by the UGT2B7 gene.

<span class="mw-page-title-main">Aldehyde oxidase</span> Enzyme

Aldehyde oxidase (AO) is a metabolizing enzyme, located in the cytosolic compartment of tissues in many organisms. AO catalyzes the oxidation of aldehydes into carboxylic acid, and in addition, catalyzes the hydroxylation of some heterocycles. It can also catalyze the oxidation of both cytochrome P450 and monoamine oxidase (MAO) intermediate products. AO plays an important role in the metabolism of several drugs.

<span class="mw-page-title-main">CYP3A5</span> Enzyme involved in drug metabolism

Cytochrome P450 3A5 is a protein that in humans is encoded by the CYP3A5 gene.

Cytochrome P450, family 3, subfamily A, also known as CYP3A, is a human gene locus. A homologous locus is found in mice.

<span class="mw-page-title-main">CYP4F2</span> Enzyme protein in the species Homo sapiens

Cytochrome P450 4F2 is a protein that in humans is encoded by the CYP4F2 gene. This protein is an enzyme, a type of protein that catalyzes chemical reactions inside cells. This specific enzyme is part of the superfamily of cytochrome P450 (CYP) enzymes, and the encoding gene is part of a cluster of cytochrome P450 genes located on chromosome 19.

<span class="mw-page-title-main">CYP2W1</span> Protein-coding gene in the species Homo sapiens

CYP2W1 is a protein that in humans is encoded by the CYP2W1 gene.

<span class="mw-page-title-main">CYP2A7</span> Protein-coding gene in the species Homo sapiens

CYP2A7 is a protein that in humans is encoded by the CYP2A7 gene.

<span class="mw-page-title-main">Hydroxybupropion</span> Group of stereoisomers

Hydroxybupropion, or 6-hydroxybupropion, is the major active metabolite of the antidepressant and smoking cessation drug bupropion. It is formed from bupropion by the liver enzyme CYP2B6 during first-pass metabolism. With oral bupropion treatment, hydroxybupropion is present in plasma at area under the curve concentrations that are as many as 16–20 times greater than those of bupropion itself, demonstrating extensive conversion of bupropion into hydroxybupropion in humans. As such, hydroxybupropion is likely to play a very important role in the effects of oral bupropion, which could accurately be thought of as functioning largely as a prodrug to hydroxybupropion. Other metabolites of bupropion besides hydroxybupropion include threohydrobupropion and erythrohydrobupropion.

<span class="mw-page-title-main">Azamulin</span> Antibiotic

Azamulin is a pleuromutilin antibiotic. As of 2021, it is not marketed in the US or Europe.

<span class="mw-page-title-main">Didesmethylsibutramine</span> Chemical compound

Didesmethylsibutramine is an active metabolite of the anorectic drug sibutramine that has been identified as an adulterant in weight loss supplements. Data on the activity of didesmethylsibutramine in humans is limited, although a case of psychosis associated with didesmethylsibutramine use was reported in 2019.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000197408 Ensembl, May 2017
  2. 1 2 3 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. 1 2 3 4 PD-icon.svg This article incorporates public domain material from "Entrez Gene: cytochrome P450". Reference Sequence collection . National Center for Biotechnology Information.
  6. 1 2 3 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. 1 2 3 4 5 6 7 8 9 10 11 12 13 Swedish environmental classification of pharmaceuticals - FASS (drug catalog) - Facts for prescribers (Fakta för förskrivare). Retrieved July 2011
  8. 1 2 3 4 5 6 7 8 9 10 11 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. 1 2 3 4 5 6 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. doi:10.1002/j.1875-9114.1997.tb03087.x. PMID   9399606. S2CID   20269145.
  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. 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.
  18. 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.
  19. 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.
  20. 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.
  21. 1 2 3 4 5 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.
  22. 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

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