CLONING, TISSUE DISTRIBUTION, AND FUNCTIONAL EXPRESSION OF 2 NOVEL RABBIT CYTOCHROME-P450 ISOZYMES, CYP2D23 AND CYP2D24

We cloned two novel cytochrome P450 cDNAs (CYP2D23 and CYP2D24) from a rabbit liver cDNA library. The open-reading frames of these cDNAs enc ode proteins that are each composed of 500 amino acids. The amino acid sequence identity of CYP2D23 with CYP2D24 is 91.6%, and the homology of these two isozymes with other known mammalian CYPs in the CYP2D sub family range from 64.9 to 79.8%, Using RT-PCR, we determined the distr ibution of these two isozymes in 9 major organs, including brain tissu e sections. CYP2D23 mRNA was abundantly expressed in the liver and sma ll intestine, but only slightly in the brain sections, whereas CYP2D24 mRNA was expressed in the liver, small intestine, and stomach, CYP2D2 3 and CYP2D24 were heterogeneously expressed in 293T cells. CYP2D24 ef fectively catalyzed the oxidation of bufuralol and bunitrolol, the arc hetypal substrates of the CYP2D subfamily, while CYP2D23 exhibited cat alytic activity only toward bufuralol, The results of this first study on rabbit CYP2D isozymes indicate that CYP2D23 and CYP2D24 are functi onally expressed in rabbits, and have different organ distributions an d metabolic properties.