Cytochrome P450 family 2 subfamily C member 19 (CYP2C19) (CYP2C19)

Cytochrome P450 family 2 subfamily C member 19 (CYP2C19) is a critical hepatic enzyme belonging to the cytochrome P450 superfamily, primarily localized in the endoplasmic reticulum of liver cells [1, 6, 13]. It plays a pivotal role in the Phase I metabolism of approximately 10-15% of clinically used drugs, including antiplatelets, proton pump inhibitors, and antidepressants [7, 12, 14]. CYP2C19 is highly polymorphic, with genetic variations significantly impacting enzyme activity and leading to distinct phenotypes ranging from poor to ultra-rapid metabolizers [8, 12]. These variations are clinically significant, particularly for the activation of the prodrug clopidogrel, where loss-of-function alleles increase the risk of major adverse cardiovascular events [10, 11]. Consequently, CYP2C19 is a primary focus of pharmacogenetic testing to optimize drug selection and dosing, thereby improving therapeutic efficacy and minimizing safety concerns like toxicity or treatment failure [11, 12].

Other names

Mephenytoin 4-hydroxylase(S)-mephenytoin 4-hydroxylaseP450-mephenytoin hydroxylaseCP2CJ

CYP2C19 catalyzes the oxidative metabolism of substrates, typically through hydroxylation or epoxidation, using molecular oxygen and electrons from NADPH via cytochrome P450 reductase [2, 12]. It acts as an activating enzyme for prodrugs like clopidogrel, converting them into their active metabolites, and as an inactivating enzyme for other drugs like amitriptyline and omeprazole, facilitating their elimination [7, 8, 13].