cDNA cloning and expression of a novel cytochrome P450 (CYP4F12) from human small intestine

A cDNA encoding a novel human CYP4F enzyme (designated CYP4F12) was cloned by PCR from a human small intestine cDNA library. RT-PCR analysis demonstra ted that CYP4F12 is expressed in human small intestine and liver. This cDNA contains an entire coding region of a 524-amino-acid protein that is 81.7, 78.3, and 78.2% identical to CYP4F2, CYP4F3, and CYP4F8, respectively. Whe n expressed in Saccharomyces cerevisiae, the P450 catalyzes leukotriene B-4 omega -hydroxylation and arachidonic acid omega -hydroxylation, typical re actions of CYP4F isoforms. Their activity levels are, however, much lower t han those of CYP4F2. Interestingly, CYP4F12 catalyzes the hydroxylation of the antihistamine ebastine with significantly higher catalytic activity rel ative to CYP4F2 (385 vs 5 pmol/min/nmol P450). These results indicate that CYP4F12 has a different profile of substrate specificity from other CYP4F i soforms, enzymes responsible for metabolizing endogenous autacoids, therefo re suggesting that it may play an important role in xenobiotic biotransform ation in the human Small intestine. (C) zool Academic Press.