Estimated kinetic parameters for dextromethorphan O- and N-demethylation catalyzed by CYP2D6, HT-CYP2D6, HT-Cyp2d22, and CYP3A4 isozymes
Each data point used to calculate kinetic constants was based on an average of duplicate determinations. Enzyme Michaelis-Menten parameters and error estimates thereof were generated by nonlinear regression analysis (GraphPad Prism 3.02).
Reaction | P450 Isoform | Vmax | Km | Vmax/Km |
|---|---|---|---|---|
| pmol/pmol P450/min | μM | nl/pmol P450/min | ||
| CYP2D6 | 13.9 ± 0.4 | 5.1 ± 0.7 | 2700 | |
| Dextromethorphan | HT-CYP2D6 | 7.8 ± 0.4 | 4.2 ± 0.7 | 1900 |
| O-Demethylation | HT-Cyp2d22 | 7.7 ± 0.4 | 250 ± 30 | 31 |
| CYP3A4 | 5.6 ± 0.1 | 170 ± 10 | 33 | |
| CYP2D6 | 55.3 ± 15.8 | 3900 ± 1700 | 14 | |
| Dextromethorphan | HT-CYP2D6 | 69.7 ± 6.6 | 4800 ± 900 | 15 |
| N-Demethylation | HT-Cyp2d22 | 20.4 ± 1.3 | 420 ± 60 | 49 |
|
| CYP3A4 | 24.5 ± 0.4 | 300 ± 20 | 81 |