CYP2C19: Difference between revisions
No edit summary |
m (Bot: Automated text replacement (-{{SIB}} + & -{{EH}} + & -{{EJ}} + & -{{Editor Help}} + & -{{Editor Join}} +)) |
||
| Line 4: | Line 4: | ||
{{SI}} | {{SI}} | ||
==Overview== | ==Overview== | ||
'''Cytochrome P450 2C19''' (abbreviated '''CYP2C19'''), a member of the [[cytochrome P450]] mixed-function oxidase system, is involved in the metabolism of [[xenobiotic]]s in the body. It is involved in the metabolism of several | '''Cytochrome P450 2C19''' (abbreviated '''CYP2C19'''), a member of the [[cytochrome P450]] mixed-function oxidase system, is involved in the metabolism of [[xenobiotic]]s in the body. It is involved in the metabolism of several | ||
| Line 125: | Line 125: | ||
{{Cytochrome P450}} | {{Cytochrome P450}} | ||
[[Category:Cytochrome P450]] | [[Category:Cytochrome P450]] | ||
Revision as of 23:19, 8 August 2012
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
|
WikiDoc Resources for CYP2C19 |
|
Articles |
|---|
|
Most recent articles on CYP2C19 |
|
Media |
|
Evidence Based Medicine |
|
Clinical Trials |
|
Ongoing Trials on CYP2C19 at Clinical Trials.gov Clinical Trials on CYP2C19 at Google
|
|
Guidelines / Policies / Govt |
|
US National Guidelines Clearinghouse on CYP2C19
|
|
Books |
|
News |
|
Commentary |
|
Definitions |
|
Patient Resources / Community |
|
Directions to Hospitals Treating CYP2C19 Risk calculators and risk factors for CYP2C19
|
|
Healthcare Provider Resources |
|
Causes & Risk Factors for CYP2C19 |
|
Continuing Medical Education (CME) |
|
International |
|
|
|
Business |
|
Experimental / Informatics |
Overview
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 clopidogrel many proton pump inhibitors and antiepileptics. In humans, the CYP2C19 protein is encoded by the CYP2C19 gene.[1][2]
CYP2C19 has been annotated as (R)-limonene 6-monooxygenase and (S)-limonene 6-monooxygenase in UniProt.
The inability to metabolize clopidogrel, or clopidogrel resistance, has been attributed, at least in part (about 11%), to genetic variations in Cytochrome P450 2C19.
Function
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.[3]
Genetic polymorphism and pharmacogenomics
Genetic polymorphism (mainly CYP2C19*2, CYP2C19*3 and CYP2C19*17) exists for CYP2C19 expression, with approximately 3–5% of Caucasian and 15–20% of Asian populations being poor metabolisers with no CYP2C19 function.[4][5]
Ligands
See also
References
- ↑ Romkes M, Faletto MB, Blaisdell JA, Raucy JL, Goldstein JA (1991). "Cloning and expression of complementary DNAs for multiple members of the human cytochrome P450IIC subfamily". Biochemistry. 30 (13): 3247–55. PMID 2009263. Unknown parameter
|month=ignored (help) - ↑ Gray IC, Nobile C, Muresu R, Ford S, Spurr NK (1995). "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. Unknown parameter
|month=ignored (help) - ↑ "Entrez Gene: CYP2C19 cytochrome P450, family 2, subfamily C, polypeptide 19".
- ↑ Bertilsson L (1995). "Geographical/interracial differences in polymorphic drug oxidation. Current state of knowledge of cytochromes P450 (CYP) 2D6 and 2C19". Clin Pharmacokinet. 29 (3): 192–209. PMID 8521680. Unknown parameter
|month=ignored (help) - ↑ Desta Z, Zhao X, Shin JG, Flockhart DA (2002). "Clinical significance of the cytochrome P450 2C19 genetic polymorphism". Clin Pharmacokinet. 41 (12): 913–58. PMID 12222994.
- ↑ Where classes of agents are listed, there may be exceptions within the class
- ↑ 7.0 7.1 Mentioned both in the reference named FASS and were previously mentioned in Wikipedia. Further contributions may follow other systems
- ↑ Zhang Y, Si D, Chen X, Lin N, Guo Y, Zhou H, Zhong D (2007). "Influence of CYP2C9 and CYP2C19 genetic polymorphisms on pharmacokinetics of gliclazide MR in Chinese subjects". Br J Clin Pharmacol. 64 (1): 67–74. doi:10.1111/j.1365-2125.2007.02846.x. PMC 2000619. PMID 17298483. Unknown parameter
|month=ignored (help) - ↑ Xu H, Williams KM, Liauw WS, Murray M, Day RO, McLachlan AJ (2008). "Effects of St John's wort and CYP2C9 genotype on the pharmacokinetics and pharmacodynamics of gliclazide". Br. J. Pharmacol. 153 (7): 1579–86. doi:10.1038/sj.bjp.0707685. PMID 18204476. Unknown parameter
|month=ignored (help) - ↑ 10.0 10.1 Flockhart, DA (2007). "Drug Interactions: Cytochrome P450 Drug Interaction Table". Indiana University School of Medicine. Retrieved on December 25, 2008.
- ↑ 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.