抄録
A cDNA of CYP2D29 was cloned from Japanese monkey (JM) livers. Its deduced amino acid sequence exhibited 96% homology to that of human CYP2D6, which was higher than the values of Cynomolgus monkey CYP2D17 (93%) and Marmoset CYP2D19 (91%). CYP2D29 protein was expressed in yeast cells, and the microsomal oxidation activities towards debrisoquine (DB), bunitrolol (BTL) and bufuralol (BF) were determined, and compared with those of recombinant CYP2D6, and of JM and human liver microsomes (Ms). For DB 4-hydroxylation, recombinant CYP2D29 and CYP2D6 showed similar Km and Vmax values, whereas the Km value of JM liver Ms was 20 times that of recombinant CYP2D29. JM liver microsomal DB 4-hydroxylase was markedly inhibited by quinidine and anti-rat CYP2D2 antibody. A similar tendency in the kinetic parameters was observed in BTL 4-hydroxylation, but Km values for BF 1″-hydroxylation were similar between recombinant CYP2D29 and JM liver Ms. These results suggest that the oxidation of DB and BTL in JM livers is mediated not only by CYP2D29 but also by another CYP(2D) enzyme. The usefulness of the monkey as a model of human in drug metabolism study will be discussed.
