Figure 8.

New paradigm for hydrolysis of EETs. Cytochrome P450 epoxygenases are localized to the cytoplasmic face of the endoplasmic reticulum adjacent to EPHX1. EPHX2 is predominantly cytoplasmic. When EET formation occurs at low rates (e.g. basal conditions), EPHX1 can hydrolyze most of the EETs as they are formed; EPHX2 contributes minimally. However, when EET production rates are high (e.g. postischemic reperfusion), EPHX1 capacity is overwhelmed and EPHX2 then contributes significantly to EET hydrolysis.