Cytochrome P450 epoxygenase (CYP epoxygenase) (CYP epoxygenase)

Cytochrome P450 (CYP) epoxygenases are a specialized group of heme-containing enzymes, primarily from the CYP2C and CYP2J subfamilies, that catalyze the NADPH-dependent epoxidation of polyunsaturated fatty acids (Spector & Norris, 2007; UniProt). Their primary endogenous substrate is arachidonic acid, which they convert into four regioisomeric epoxyeicosatrienoic acids (EETs): 5,6-, 8,9-, 11,12-, and 14,15-EET (Zeldin, 2001; NCBI). These EETs function as autocrine and paracrine signaling molecules that mediate vital physiological processes, including vasodilation, inhibition of platelet aggregation, and anti-inflammatory effects within the vascular wall (Imig, 2012; PubMed). Consequently, CYP epoxygenases play a protective role in the cardiovascular system, and their dysfunction is implicated in the pathogenesis of hypertension, myocardial infarction, and stroke (Capdevila & Falck, 2001; NIH). In the context of oncology, certain epoxygenases like CYP2J2 are frequently overexpressed in human cancers, where they promote tumor cell proliferation and metastasis by stimulating angiogenesis (Jiang et al., 2007; PubMed). Pharmacological targeting of these enzymes involves both the development of inhibitors for cancer therapy and the use of soluble epoxide hydrolase (sEH) inhibitors to stabilize the beneficial EETs produced by these enzymes for treating cardiovascular and inflammatory diseases (Wagner et al., 2011; StatPearls).

Other names

Arachidonic acid epoxygenaseCYP2CCYP2JFatty acid epoxygenaseP450 epoxygenaseCytochrome P450 2C8Cytochrome P450 2C9Cytochrome P450 2J2

Modulation of the arachidonic acid cascade to alter the levels of epoxyeicosatrienoic acids (EETs), which act as potent lipid mediators in vascular and inflammatory signaling.