CYP2C19

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.

PBB_Summary
section_title =
summary_text = This gene encodes a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases that 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. [cite web | title = Entrez Gene: CYP2C19 cytochrome P450, family 2, subfamily C, polypeptide 19| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1557| accessdate = ]

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

See also

*Cytochrome P450 oxidase

References

Further reading

PBB_Further_reading
citations =
*cite journal | author=Goldstein JA, de Morais SM |title=Biochemistry and molecular biology of the human CYP2C subfamily. |journal=Pharmacogenetics |volume=4 |issue= 6 |pages= 285–99 |year= 1995 |pmid= 7704034 |doi=
*cite journal | author=Smith G, Stubbins MJ, Harries LW, Wolf CR |title=Molecular genetics of the human cytochrome P450 monooxygenase superfamily. |journal=Xenobiotica |volume=28 |issue= 12 |pages= 1129–65 |year= 1999 |pmid= 9890157 |doi=
*cite journal | author=Ding X, Kaminsky LS |title=Human extrahepatic cytochromes P450: function in xenobiotic metabolism and tissue-selective chemical toxicity in the respiratory and gastrointestinal tracts. |journal=Annu. Rev. Pharmacol. Toxicol. |volume=43 |issue= |pages= 149–73 |year= 2003 |pmid= 12171978 |doi= 10.1146/annurev.pharmtox.43.100901.140251
*cite journal | author=Romkes M, Faletto MB, Blaisdell JA, "et al." |title=Cloning and expression of complementary DNAs for multiple members of the human cytochrome P450IIC subfamily. |journal=Biochemistry |volume=30 |issue= 13 |pages= 3247–55 |year= 1991 |pmid= 2009263 |doi=
*cite journal | author=Meier UT, Meyer UA |title=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. |journal=Biochemistry |volume=26 |issue= 25 |pages= 8466–74 |year= 1988 |pmid= 3442670 |doi=
*cite journal | author=De Morais SM, Wilkinson GR, Blaisdell J, "et al." |title=Identification of a new genetic defect responsible for the polymorphism of (S)-mephenytoin metabolism in Japanese. |journal=Mol. Pharmacol. |volume=46 |issue= 4 |pages= 594–8 |year= 1994 |pmid= 7969038 |doi=
*cite journal | author=Romkes M, Faletto MB, Blaisdell JA, "et al." |title=Cloning and expression of complementary DNAs for multiple members of the human cytochrome PH50IIC subfamily. |journal=Biochemistry |volume=32 |issue= 5 |pages= 1390 |year= 1993 |pmid= 8095407 |doi=
*cite journal | author=Goldstein JA, Faletto MB, Romkes-Sparks M, "et al." |title=Evidence that CYP2C19 is the major (S)-mephenytoin 4'-hydroxylase in humans. |journal=Biochemistry |volume=33 |issue= 7 |pages= 1743–52 |year= 1994 |pmid= 8110777 |doi=
*cite journal | author=de Morais SM, Wilkinson GR, Blaisdell J, "et al." |title=The major genetic defect responsible for the polymorphism of S-mephenytoin metabolism in humans. |journal=J. Biol. Chem. |volume=269 |issue= 22 |pages= 15419–22 |year= 1994 |pmid= 8195181 |doi=
*cite journal | author=Gray IC, Nobile C, Muresu R, "et al." |title=A 2.4-megabase physical map spanning the CYP2C gene cluster on chromosome 10q24. |journal=Genomics |volume=28 |issue= 2 |pages= 328–32 |year= 1996 |pmid= 8530044 |doi= 10.1006/geno.1995.1149
*cite journal | author=Karam WG, Goldstein JA, Lasker JM, Ghanayem BI |title=Human CYP2C19 is a major omeprazole 5-hydroxylase, as demonstrated with recombinant cytochrome P450 enzymes. |journal=Drug Metab. Dispos. |volume=24 |issue= 10 |pages= 1081–7 |year= 1997 |pmid= 8894508 |doi=
*cite journal | author=Xiao ZS, Goldstein JA, Xie HG, "et al." |title=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. |journal=J. Pharmacol. Exp. Ther. |volume=281 |issue= 1 |pages= 604–9 |year= 1997 |pmid= 9103550 |doi=
*cite journal | author=Guengerich FP, Johnson WW |title=Kinetics of ferric cytochrome P450 reduction by NADPH-cytochrome P450 reductase: rapid reduction in the absence of substrate and variations among cytochrome P450 systems. |journal=Biochemistry |volume=36 |issue= 48 |pages= 14741–50 |year= 1998 |pmid= 9398194 |doi= 10.1021/bi9719399
*cite journal | author=Ferguson RJ, De Morais SM, Benhamou S, "et al." |title=A new genetic defect in human CYP2C19: mutation of the initiation codon is responsible for poor metabolism of S-mephenytoin. |journal=J. Pharmacol. Exp. Ther. |volume=284 |issue= 1 |pages= 356–61 |year= 1998 |pmid= 9435198 |doi=
*cite journal | author=Ibeanu GC, Goldstein JA, Meyer U, "et al." |title=Identification of new human CYP2C19 alleles (CYP2C19*6 and CYP2C19*2B) in a Caucasian poor metabolizer of mephenytoin. |journal=J. Pharmacol. Exp. Ther. |volume=286 |issue= 3 |pages= 1490–5 |year= 1998 |pmid= 9732415 |doi=
*cite journal | author=Ibeanu GC, Blaisdell J, Ghanayem BI, "et al." |title=An additional defective allele, CYP2C19*5, contributes to the S-mephenytoin poor metabolizer phenotype in Caucasians. |journal=Pharmacogenetics |volume=8 |issue= 2 |pages= 129–35 |year= 1999 |pmid= 10022751 |doi=
*cite journal | author=Foster DJ, Somogyi AA, Bochner F |title=Methadone N-demethylation in human liver microsomes: lack of stereoselectivity and involvement of CYP3A4. |journal=British journal of clinical pharmacology |volume=47 |issue= 4 |pages= 403–12 |year= 1999 |pmid= 10233205 |doi=
*cite journal | author=Ibeanu GC, Blaisdell J, Ferguson RJ, "et al." |title=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. |journal=J. Pharmacol. Exp. Ther. |volume=290 |issue= 2 |pages= 635–40 |year= 1999 |pmid= 10411572 |doi=

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