cDNA cloning and expression of CYP4F12, a novel human cytochrome P450

cDNA of a novel human cytochrome P450 was cloned from human liver by revers e transcription-polymerase chain reaction and designated CYP4F12. The open reading frame coded for 524 amino acids, and the sequence could be aligned with 78-83% amino acid identity to the four human CYP4F enzymes (CYP4F2, CY P4F3, CYP4F8 and CYP4F11). Northern blot analysis suggested three major tra nscripts of CYP4F12, which were detected in liver, kidney, colon, small int estine and heart. The CYP4F12 gene contained 13 exons and was located at ch romosome 19p13.1. CYP4F12, expressed in yeast, oxidized arachidonic acid to 18-hydroxyarachidonic acid, and the omega -side chain of two stable prosta glandin (PG) H-2 analogs (11.9 epoxymethano-PGH(2) and 9,11-diazo-15- deoxy -PGH(2)). CYP4F12 oxidized the omega -side chain of leukotriene B-4, PGE(2) , PGF(2 alpha), PGH(2), and 9,11-epoxymethano-PGH(2) poorly. Several CYP4F enzymes are important omega1- and omega2-hydroxylases of eicosanoids. The p hysiological function of CYP4F12 merits further investigation. (C) 2001 Aca demic Press.