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cytochrome P450 2C19 (cytochrome P450 2C17, cytochrome P450 11A, mephenytoin 4-hydroxylase, cytochrome P450 254C, CYP2C19)

Function: 1) responsible for the metabolism of a number of drugs (see substrates) 2) R isoform of warfarin is a substrate of cyt P450 2C19 3) inducers - carbamazepine - Ginkgo biloba - Hypericum perforatum (St John' wort) - norethindrone - phenobarbital - phenytoin - prednisone - rifampin - ritonavir - tipranavir 4) inhibitors - chloramphenicol - cimetidine - citalopram - delavirdine - efavirenz - esomeprazole - ethinyl estradiol - etravirine - felbamate - fluconazole - fluoxetine - fluvoxamine - indomethacin - isoniazid - ketoconazole - lansoprazole - letrozole - moclobemide - modafinil - nicardipine - omeprazole - oxcarbazepine - pantoprazole - Piper methysticum (Kava-kava) - rabeprazole - sertraline - telmisartan - ticlopidine - topiramate - vilazodone - voriconazole 5) substrates - amitriptyline - aprepitant - carisoprodol - cilostazol - citalopram - clomipramine - clopidogrel - cyclophosphamide - desipramine - diazepam - escitalopram - esomeprazole - etravirine - formoterol - hexobarbital - imipramine - indomethacin - lansoprazole - lapatinib - mephobarbital - methadone - moclobemide - nelfinavir - nilutamide - omeprazole - pantoprazole - pentamidine - phenytoin - progesterone - proguanil - propranolol - rabeprazole - teniposide - thioridazine - tolbutamide - voriconazole - warfarin Compartment: membrane-bound, endoplasmic reticulum Expression: highly inducible Polymorphism: 1) genetic variation in CYP2C19 is responsible for poor drug metabolism [MIM:609535] 2) individuals can be characterized as either a) extensive metabolizers - homozygous dominant & heteroyzgous genotypes b) poor metabolizers - inherited in an autosomal recessive manner - 2-5% of Caucasians - 13-23% of Asian populations - 38-79% of individuals from Polynesia & Micronesia. 3) several-many different alleles of CYP2C19 Laboratory: - CYP2C19 enzyme activity - CYP2C19 gene mutation

Related

cyt P450 2C19 gene

General

cytochrome P450 2C (CYP2C)

Properties

SIZE: MW = 56 kD entity length = 490 aa COMPARTMENT: endoplasmic reticulum MOTIF: Iron [Fe]-binding site SITE: 435-435

Database Correlations

OMIM 124020 UniProt P33261 Pfam PF00067 Entrez Gene 1557 Kegg hsa:1557 ENZYME correlations

References

  1. UniProt :accession P33261
  2. Prescriber's Letter 13(3): 2006 Cytochrome P450 Drug Interactions Detail-Document#: 220233 (subscription needed) http://www.prescribersletter.com
  3. Cytochrome P450 Allele Nomenclature committee, CYP2C19 alleles http://www.cypalleles.ki.se/cyp2c19.htm
  4. Prescriber's Letter 17(1): 2010 Cytochrome P450 Drug Interactions CHART: Cytochrome P450 Drug Interactions COMMENTARY: Proton Pump Inhibitor and Plavix Interaction: An Update Detail-Document#: 260112 (subscription needed) http://www.prescribersletter.com
  5. Prescriber's Letter 18(3): 2011 CHART: Cytochrome P450 Drug Interactions Detail-Document#: 270307 (subscription needed) http://www.prescribersletter.com