CYP2J2 is a member of the cytochrome P450 (CYP) family of monooxygenases, and, in humans, is the ... more CYP2J2 is a member of the cytochrome P450 (CYP) family of monooxygenases, and, in humans, is the sole member of the CYP2J subfamily . Specifically, CYP2J2 is an epoxygenasethat catalyzes epoxideformation at thesite of a carbon-carbon double bond in the substrate, as other CYP epoxygenases do, such as CYP2C8 and CYP2C9 . The therapeutic agents ebastine [3], astemizole, terfenadine, diclofenac, and bufurarol are metabolized by CYP2J2 [4]. A recent study, screening 139 marketed therapeutic agents and compounds, have identified albendazole, amiodarone, cyclosporine A, danazol, mesoridazine, nabumetone, tamoxifen, and thioridazine as CYP2J2 substrates . These findings show the ability of CYP2J2 to metabolize structurally diverse compounds. The substrates identified for CYP2J2 were also metabolized by CYP3A4, but with differences in regioselectivity . For large compounds, CYP2J2 metabolism was more restricted to a single site, compared with CYP3A4, which metabolized substrates at multiple sites . A study of microsomes from human livers and human small intestines investigated the metabolism of astemizole by CYP2J2 [6]. This study found that the CYP2J2 substrates arachidonic acid (AA) and ebastine strongly inhibited astemizole O-demethylation in microsomes from human small intestines and in in-vitro experiments with recombinant CYP2J2 . A follow-up study found an inhibition of α-naphthoflavone, ketoconazole, troglitazone, tranylcypromine, ebastine, and terfenadine on the rate of astemizole Odemethylation in human small intestinal microsomes and on the rate of astemizole Odemethylation in recombinant CYP2J2 microsomes . AA and linoleic acid (LA) are endogenous substrates of CYP2J2 . CYP epoxygenases catalyze the metabolism of AA to four regioisomeric epoxyeicosatrienoic acids (EETs): 14,15-EET, 11,12-EET, 5,6-EET, and 8,9-EET [9]. EETs have been shown to possess many biologically relevant properties, such as inducing membrane hyperpolarization and vasodilation, reducing inflammation by inhibition of transcription factor nuclear factor-κB, and increasing fibrinolytic activity (reviewed in ). CYP2J2-derived EETs have been
CYP2J2 is a member of the cytochrome P450 (CYP) family of monooxygenases, and, in humans, is the ... more CYP2J2 is a member of the cytochrome P450 (CYP) family of monooxygenases, and, in humans, is the sole member of the CYP2J subfamily . Specifically, CYP2J2 is an epoxygenasethat catalyzes epoxideformation at thesite of a carbon-carbon double bond in the substrate, as other CYP epoxygenases do, such as CYP2C8 and CYP2C9 . The therapeutic agents ebastine [3], astemizole, terfenadine, diclofenac, and bufurarol are metabolized by CYP2J2 [4]. A recent study, screening 139 marketed therapeutic agents and compounds, have identified albendazole, amiodarone, cyclosporine A, danazol, mesoridazine, nabumetone, tamoxifen, and thioridazine as CYP2J2 substrates . These findings show the ability of CYP2J2 to metabolize structurally diverse compounds. The substrates identified for CYP2J2 were also metabolized by CYP3A4, but with differences in regioselectivity . For large compounds, CYP2J2 metabolism was more restricted to a single site, compared with CYP3A4, which metabolized substrates at multiple sites . A study of microsomes from human livers and human small intestines investigated the metabolism of astemizole by CYP2J2 [6]. This study found that the CYP2J2 substrates arachidonic acid (AA) and ebastine strongly inhibited astemizole O-demethylation in microsomes from human small intestines and in in-vitro experiments with recombinant CYP2J2 . A follow-up study found an inhibition of α-naphthoflavone, ketoconazole, troglitazone, tranylcypromine, ebastine, and terfenadine on the rate of astemizole Odemethylation in human small intestinal microsomes and on the rate of astemizole Odemethylation in recombinant CYP2J2 microsomes . AA and linoleic acid (LA) are endogenous substrates of CYP2J2 . CYP epoxygenases catalyze the metabolism of AA to four regioisomeric epoxyeicosatrienoic acids (EETs): 14,15-EET, 11,12-EET, 5,6-EET, and 8,9-EET [9]. EETs have been shown to possess many biologically relevant properties, such as inducing membrane hyperpolarization and vasodilation, reducing inflammation by inhibition of transcription factor nuclear factor-κB, and increasing fibrinolytic activity (reviewed in ). CYP2J2-derived EETs have been
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