CYP2C19
| Cytochrome P450, family 2, subfamily C, polypeptide 19 | |||||||||||
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 PDB rendering based on 1r9o. | |||||||||||
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| Symbols | CYP2C19 ; CPCJ; CYP 2C; CYP2C; P450C2C; P450IIC19 | ||||||||||
| External IDs | Template:OMIM5 Template:MGI HomoloGene: 86659 | ||||||||||
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| Species | Human | Mouse | |||||||||
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Cytochrome P450 2C19 (abbreviated CYP2C19), a member of the cytochrome P450 mixed-function oxidase system, is involved in the metabolism of xenobiotics in the body. It is involved in the metabolism of several important groups of drugs including many proton pump inhibitors and antiepileptics.
This gene 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 is known to metabolize many xenobiotics, including the anticonvulsive drug mephenytoin, omeprazole, diazepam and some barbiturates. Polymorphism within this gene is associated with variable ability to metabolize mephenytoin, known as the poor metabolizer and extensive metabolizer phenotypes. The gene is located within a cluster of cytochrome P450 genes on chromosome no.10 arm q24.[1]
Genetic polymorphism exists for CYP2C19 expression, with approximately 3–5% of Caucasian and 15–20% of Asian populations being poor metabolisers with no CYP2C19 function.
It has been annotated as (R)-limonene 6-monooxygenase and (S)-limonene 6-monooxygenase in UniProt.
Ligands
| Substrates | Inhibitors | Inducers |
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Often mentioned:[3]
Other: |
Strong:[4]
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Often mentioned:[3]
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See also
References
- ↑ "Entrez Gene: CYP2C19 cytochrome P450, family 2, subfamily C, polypeptide 19".
- ↑ Where classes of agents are listed, there may be exceptions within the class
- ↑ 3.0 3.1 Mentioned both in the reference named FASS and were previously mentioned in Wikipedia. Further contributions may follow other systems
- ↑ Swedish environmental classification of pharmaceuticals Facts for prescribers (Fakta för förskrivare)
Further reading
- Goldstein JA, de Morais SM (1995). "Biochemistry and molecular biology of the human CYP2C subfamily". Pharmacogenetics. 4 (6): 285–99. PMID 7704034.
- Smith G, Stubbins MJ, Harries LW, Wolf CR (1999). "Molecular genetics of the human cytochrome P450 monooxygenase superfamily". Xenobiotica. 28 (12): 1129–65. PMID 9890157.
- Ding X, Kaminsky LS (2003). "Human extrahepatic cytochromes P450: function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts". Annu. Rev. Pharmacol. Toxicol. 43: 149–73. doi:10.1146/annurev.pharmtox.43.100901.140251. PMID 12171978.
- Romkes M, Faletto MB, Blaisdell JA; et al. (1991). "Cloning and expression of complementary DNAs for multiple members of the human cytochrome P450IIC subfamily". Biochemistry. 30 (13): 3247–55. PMID 2009263.
- Meier UT, Meyer UA (1988). "Genetic polymorphism of human cytochrome P-450 (S)-mephenytoin 4-hydroxylase. Studies with human autoantibodies suggest a functionally altered cytochrome P-450 isozyme as cause of the genetic deficiency". Biochemistry. 26 (25): 8466–74. PMID 3442670.
- De Morais SM, Wilkinson GR, Blaisdell J; et al. (1994). "Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese". Mol. Pharmacol. 46 (4): 594–8. PMID 7969038.
- Romkes M, Faletto MB, Blaisdell JA; et al. (1993). "Cloning and expression of complementary DNAs for multiple members of the human cytochrome PH50IIC subfamily". Biochemistry. 32 (5): 1390. PMID 8095407.
- Goldstein JA, Faletto MB, Romkes-Sparks M; et al. (1994). "Evidence that CYP2C19 is the major (S)-mephenytoin 4'-hydroxylase in humans". Biochemistry. 33 (7): 1743–52. PMID 8110777.
- de Morais SM, Wilkinson GR, Blaisdell J; et al. (1994). "The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans". J. Biol. Chem. 269 (22): 15419–22. PMID 8195181.
- Gray IC, Nobile C, Muresu R; et al. (1996). "A 2.4-megabase physical map spanning the CYP2C gene cluster on chromosome 10q24". Genomics. 28 (2): 328–32. doi:10.1006/geno.1995.1149. PMID 8530044.
- Karam WG, Goldstein JA, Lasker JM, Ghanayem BI (1997). "Human CYP2C19 is a major omeprazole 5-hydroxylase, as demonstrated with recombinant cytochrome P450 enzymes". Drug Metab. Dispos. 24 (10): 1081–7. PMID 8894508.
- Xiao ZS, Goldstein JA, Xie HG; et al. (1997). "Differences in the incidence of the CYP2C19 polymorphism affecting the S-mephenytoin phenotype in Chinese Han and Bai populations and identification of a new rare CYP2C19 mutant allele". J. Pharmacol. Exp. Ther. 281 (1): 604–9. PMID 9103550.
- Guengerich FP, Johnson WW (1998). "Kinetics of ferric cytochrome P450 reduction by NADPH-cytochrome P450 reductase: rapid reduction in the absence of substrate and variations among cytochrome P450 systems". Biochemistry. 36 (48): 14741–50. doi:10.1021/bi9719399. PMID 9398194.
- Ferguson RJ, De Morais SM, Benhamou S; et al. (1998). "A new genetic defect in human CYP2C19: mutation of the initiation codon is responsible for poor metabolism of S-mephenytoin". J. Pharmacol. Exp. Ther. 284 (1): 356–61. PMID 9435198.
- Ibeanu GC, Goldstein JA, Meyer U; et al. (1998). "Identification of new human CYP2C19 alleles (CYP2C19*6 and CYP2C19*2B) in a Caucasian poor metabolizer of mephenytoin". J. Pharmacol. Exp. Ther. 286 (3): 1490–5. PMID 9732415.
- Ibeanu GC, Blaisdell J, Ghanayem BI; et al. (1999). "An additional defective allele, CYP2C19*5, contributes to the S-mephenytoin poor metabolizer phenotype in Caucasians". Pharmacogenetics. 8 (2): 129–35. PMID 10022751.
- Foster DJ, Somogyi AA, Bochner F (1999). "Methadone N-demethylation in human liver microsomes: lack of stereoselectivity and involvement of CYP3A4". British journal of clinical pharmacology. 47 (4): 403–12. PMID 10233205.
- Ibeanu GC, Blaisdell J, Ferguson RJ; et al. (1999). "A novel transversion in the intron 5 donor splice junction of CYP2C19 and a sequence polymorphism in exon 3 contribute to the poor metabolizer phenotype for the anticonvulsant drug S-mephenytoin". J. Pharmacol. Exp. Ther. 290 (2): 635–40. PMID 10411572.