CYP2C19

Cytochrome P450 2C19 (abbreviated CYP2C19) is an is_associated_with::enzyme. This is_associated_with::protein, a member of the is_associated_with::cytochrome P450 mixed-function oxidase system, is involved in the metabolism of is_associated_with::xenobiotics, including many is_associated_with::proton pump inhibitors and is_associated_with::antiepileptics. In humans, the CYP2C19 protein is encoded by the CYP2C19 is_associated_with::gene. CYP2C19 is a liver enzyme that acts on 10-15% of drugs in current clinical use, including the antiplatelet is_associated_with::clopidogrel (Plavix), antiulcer drugs such as is_associated_with::omeprazole, antiseizure drugs such as is_associated_with::mephenytoin, the antimalarial is_associated_with::proguanil, and the anxiolytic is_associated_with::diazepam.

CYP2C19 has been annotated as is_associated_with::(R)-limonene 6-monooxygenase and is_associated_with::(S)-limonene 6-monooxygenase in is_associated_with::UniProt.

Function
The gene encodes a member of the cytochrome P450 superfamily of enzymes. These proteins are is_associated_with::monooxygenases that catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. This protein localizes to the is_associated_with::endoplasmic reticulum and is known to metabolize many drugs. 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.

Genetic polymorphism and pharmacogenomics
is_associated_with::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 metabolizers with no CYP2C19 function. This may reduce the efficacy of clopidogrel (Plavix). In patients with an abnormal CYP2C19 variant certain is_associated_with::benzodiazepines should be avoided, such as diazepam (Valium), is_associated_with::lorazepam (Ativan), is_associated_with::oxazepam (Serax), and is_associated_with::temazepam (Restoril). On the basis of their ability to metabolize (S)-mephenytoin or other CYP2C19 substrates, individuals can be classified as extensive metabolizers (EM) or poor metabolizers (PM). Eight variant alleles (CYP2C19*2 to CYP2C19*8) that predict PMs have been identified.

Ligands
The following is a table of selected substrates, inducers and inhibitors of CYP2C19. Where classes of agents are listed, there may be exceptions within the class.

Inhibitors of CYP2C19 can be classified by their potency, such as:
 * Strong being one that causes at least a 5-fold increase in the plasma AUC values, or more than 80% decrease in clearance.
 * Moderate being one that causes at least a 2-fold increase in the plasma AUC values, or 50-80% decrease in clearance.
 * Weak being one that causes at least a 1.25-fold but less than 2-fold increase in the plasma AUC values, or 20-50% decrease in clearance.