Novel cytochrome P450 2J isoforms in tree shrews are functional drug-metabolising enzymes involved in ebastine and astemizole oxidation

The cytochromes P450 (P450 or CYP), a family of drug-metabolising enzymes, are important in drug development and drug therapy. In tree shrews, a range of P450s, including CYP1A, CYP2A, CYP2B, CYP2C, CYP2D, CYP2E, CYP3A, CYP4A, and CYP4F, have been identified and analysed. In general tree shrew P450s have enzymatic characteristics similar to those of human P450s.In the present study, the cDNAs of five novel tree shrew P450s homologous to human CYP2J2, namely, CYP2J104, CYP2J105, CYP2J106, CYP2J107, and CYP2J108, were identified. The deduced amino acid sequences (500–502 residues) were highly homologous (79–87%) to human CYP2J2 and were closely related to human CYP2J2 in a phylogenetic tree.All five novel tree shrew CYP2J genes contained nine coding exons and formed a gene cluster at a genomic region corresponding to human CYP2J2. Except for CYP2J104 mRNA, expression of all tree shrew CYP2J2 mRNAs was detected in liver.All five tree shrew CYP2Js metabolised ebastine and astemizole, typical substrates of human CYP2J2, and thus were functional enzymes with characteristics similar to human CYP2J2.