Cytochrome P450 2J2 (CYP2J2) (CYP2J2)

Cytochrome P450 2J2 (CYP2J2) is a heme-thiolate monooxygenase and the sole functional member of the human CYP2J subfamily, highly expressed in the heart, vascular endothelium, and small intestine (UniProt: P51589, PMC: 2829215). It primarily functions as an epoxygenase, converting arachidonic acid into four regioisomeric epoxyeicosatrienoic acids (EETs) that regulate vascular tone, promote angiogenesis, and exert potent anti-inflammatory and cardioprotective effects (PubMed: 8631948, PMC: 6010146). Beyond its homeostatic roles, CYP2J2 is a significant drug-metabolizing enzyme involved in the oxidation of various clinical agents, such as antihistamines, anticancer drugs, and immunosuppressants (PubMed: 19923256, PMC: 3444652). The target has significant clinical relevance in both cardiovascular medicine and oncology. While CYP2J2-derived EETs protect against myocardial injury and hypertension, the enzyme's overexpression in several malignant tumors promotes cancer cell proliferation, migration, and resistance to apoptosis, making it a potential therapeutic target for cancer inhibition (PubMed: 34162468, PMC: 2613560). Furthermore, because many drugs that inhibit CYP2J2 are associated with cardiotoxicity or a risk of Torsades de Pointes, it serves as a critical biomarker for assessing drug safety and potential drug-drug interactions (PubMed: 37528434, PMC: 3444652). Genetic polymorphisms, such as the CYP2J2*7 variant, are also studied as biomarkers for susceptibility to coronary artery disease and hypertension (PubMed: 17296645).

Other names

CPJ2CYPIIJ2Arachidonic acid epoxygenaseCytochrome P450 family 2 subfamily J member 2

Cytochrome P450 2J2 acts as a dual-function monooxygenase and epoxygenase. It catalyzes the NADPH-dependent epoxidation of polyunsaturated fatty acids (PUFAs), converting arachidonic acid into four regioisomeric epoxyeicosatrienoic acids (EETs: 5,6-, 8,9-, 11,12-, and 14,15-EET) that modulate vascular tone and provide cardioprotection via K+ channel activation and anti-inflammatory signaling. It also mediates the phase I oxidative metabolism of various therapeutic drugs, potentially leading to drug-drug interactions or cardiotoxicity when inhibited.