Microsomes prepared from COS-1 cells transiently expressing rabbit cytochromes 
P450 2C1 and 2C2 catalyzed the metabolism of arachidonic acid to predominantly 
11,12- and 14,15-epoxyeicosatrienoic acids (EETs) when microsomal epoxide 
hydrolase activity was inhibited by 0.2 mM 1,2-epoxy-3,3,3-trichloropropane. 
P450 2C2 catalyzed the formation of 11,12-EET and 14,15-EET at a ratio of 3.0 
and also produced 19-hydroxyeicosatetraenoic acid (19-HETE). The 11,12-EET, 
14,15-EET, and 19-HETE represented 48.3, 15.9, and 12.8%, respectively, of the 
total metabolites formed. P450 2C1 produced a similar but distinct ratio of 
11,12-EET to 14,15-EET (2.0) and did not produce any detectable 19-HETE. The 
11,12-EET and 14,15-EET represented 63.0 and 31.1%, respectively, of the total 
metabolites formed. The 8,9- and 5,6-EETs were not detected with either enzyme. 
The ratio of the 11,12-EET to 14,15-EET was 1.5 with P450 2CAA, a P450 
arachidonic acid epoxygenase (P450 2CAA) that had an amino-terminal sequence 
identical to that of P450 2C2 [J. Biol. Chem. 267:5552-5559 (1992)]. P450 2C1, 
2C2, and 2CAA metabolized lauric acid. The ratio of omega-1- to 
omega-hydroxylated laurate was 3.6, 3.4, and 2.4 for P450 2CAA, P450 2C2, and 
P450 2C1, respectively. Purified P450 2CAA had a slightly greater apparent 
molecular weight than expressed P450 2C2 on sodium dodecyl 
sulfate-polyacrylamide gels. The results clearly establish that rabbit P450 2C1 
and 2C2 are arachidonic acid epoxygenases, and they suggest that P450 2CAA and 
2C2 are very similar but may not be identical isoforms.