the in vivo ability and significance of 19-HETE in inhibiting 20-HETE has not been demonstrated (see 20-Hydroxyeicosatetraenoic acid). The EDP (see Epoxydocosapentaenoic acid) and EEQ (see epoxyeicosatetraenoic acid) metabolites have a broad range of activities. In various animal models and in vitro studies on animal and human tissues, they decrease hypertension and pain perception; suppress inflammation; inhibit angiogenesis, endothelial cell migration and endothelial cell proliferation; and inhibit the growth and metastasis of human breast and prostate cancer cell lines. It is suggested that the EDP and EEQ metabolites function in humans as they do in animal models and that, as products of the omega-3 fatty acids, docosahexaenoic acid and eicosapentaenoic acid, the EDP and EEQ metabolites contribute to many of the beneficial effects attributed to dietary omega-3 fatty acids. EDP and EEQ metabolites are short-lived, being inactivated within seconds or minutes of formation by epoxide hydrolases, particularly soluble epoxide hydrolase, and therefore act locally. CYP2E1 is not regarded as being a major contributor to forming the cited epoxides but could act locally in certain tissues to do so. Substrates Following is a table of selected substrates of CYP2E1. Where classes of agents are listed, there may be exceptions within the class. Structure CYP2E1 exhibits structural motifs common to other human membrane-bound cytochrome P450 enzymes, and is composed of 12 major α-helices and 4 β-sheets with short intervening helices interspersed between the two. Like other enzymes of this class, the active site of CYP2E1 contains an iron atom bound by a heme center which mediates the electron transfer steps necessary to carry out oxidation of its substrates. The active site of CYP2E1 is the smallest observed in human P450 enzymes, with its small capacity attributed in part to the introduction of an isoleucine at position 115. The side-chain of this residue protrudes out above the heme center, restricting active site volume compared to related enzymes that have less bulky residues at this position. T303, which also protrudes into the active site, is particularly important for substrate positioning above the reactive iron center and is hence highly conserved by many cytochrome P450 enzymes. Its hydroxyl group is well-positioned to donate a hydrogen bond to potential acceptors on the substrate, and its methyl group has also been implicated in the positioning of fatty acids within the active site., A number of residues proximal to the active site including L368 help make up a