PT  - JOURNAL ARTICLE
AU  - S V Otton
AU  - R F Tyndale
AU  - D Wu
AU  - T Inaba
AU  - W Kalow
AU  - E M Sellers
TI  - Catalytic and immunologic similarities between monkey and human liver cytochrome P-450db1 (human cytochrome P-450 2D6).
DP  - 1992 Jan 01
TA  - Drug Metabolism and Disposition
PG  - 1--5
VI  - 20
IP  - 1
4099  - http://dmd.aspetjournals.org/content/20/1/1.short
4100  - http://dmd.aspetjournals.org/content/20/1/1.full
SO  - Drug Metab Dispos1992 Jan 01; 20
AB  - In vivo pharmacogenetic studies have suggested that the monkey may be an animal model for the human polymorphism of cytochrome P-450 2D6 (also called cytochrome P-450db1). In the present study, the catalytic, immunologic, and electrophoretic properties of cytochrome P-450db1 in liver microsomes from African green monkeys (Cercopithecus aethiops) were examined and compared with P-450db1 in human liver microsomes. Using sparteine as the substrate, the activity of microsomal P-450db1 from the two sources was indistinguishable in terms of the pattern of sparteine metabolites produced, the apparent Ki values of 8 competitive inhibitors (r = 0.94, p less than 0.001), and the extent of immunoinhibition by anti-rat P-450db1 antibody. Kinetic analyses demonstrated that the apparent KM values of the high affinity component of sparteine oxidation in monkey liver microsomes fell within the range observed in human livers; the Vmax of this component was as much as six times greater than the highest value reported for human liver. Western immunoblots showed a protein band in monkey liver microsomes that co-migrated with P-450db1 in human liver. The high degree of similarity observed here between P-450db1 of monkey and human liver microsomes suggests that the monkey will be a good animal model for P-450db1 enzyme studies, and possibly for studies of the role of this enzyme in drug abuse and dependence.