Kinetic parameters for MPTP oxidation by marmoset and human liver microsomes and recombinant CYP2D6 and FMO3
Kinetic parameters were calculated by nonlinear regression analysis (mean ± S.E., 10 points of substrate concentrations within the range 1–2000 μM).
| Kinetic Parameter | Marmoset | Human | ||||
|---|---|---|---|---|---|---|
| Liver Microsomes | CYP2D6 | FMO3 | Liver Microsomes | CYP2D6 | FMO3 | |
| PTP formation | ||||||
| Km (μM) | 451 ± 99 | 71 ± 7 | N.A. | 577 ± 116 | 125 ± 23 | N.A. |
| Vmax (nmol/min per mg) | 0.43 ± 0.03 | — | — | 0.13 ± 0.01 | — | — |
| Vmax (min−1) | — | 15.6 ± 0.4 | <0.01 | — | 11.5 ± 0.6 | <0.01 |
| Vmax/Km (μl/min per mg) | 0.95 | — | — | 0.23 | — | — |
| Vmax/Km (μl/min per nmol) | — | 220 | N.A. | — | 92 | N.A. |
| MPTP N-oxide formation | ||||||
| Km (μM) | 162 ± 21 | N.A. | 137 ± 14 | 173 ± 69 | N.A. | 102 ± 19 |
| Vmax (nmol/min per mg) | 0.52 ± 0.02 | — | — | 0.22 ± 0.02 | — | — |
| Vmax (min−1) | — | <0.1 | 23 ± 1 | — | <0.1 | 104 ± 5 |
| Vmax/Km (μl/min per mg) | 3.2 | — | — | 1.3 | — | — |
| Vmax/Km (ml/min per nmol) | — | N.A. | 0.17 | — | N.A. | 1.0 |
| MPDP+ formation | ||||||
| Km (μM) | 125 ± 19 | 74 ± 23 | N.A. | 103 ± 6 | 276 ± 96 | N.A. |
| Vmax (nmol/min per mg) | 0.23 ± 0.01 | — | — | 0.66 ± 0.01 | — | — |
| Vmax (min−1) | — | 5.5 ± 0.4 | <0.1 | — | 1.0 ± 0.1 | <0.1 |
| Vmax/Km (μl/min per mg) | 1.8 | — | — | 6.4 | — | — |
| Vmax/Km (μl/min per nmol) | — | 74 | N.A. | — | 3.6 | N.A. |
| MPP+ formation | ||||||
| Km (μM) | 66 ± 18 | 72 ± 18 | N.A. | 53 ± 10 | 331 ± 110 | N.A. |
| Vmax (nmol/min per mg) | 0.23 ± 0.02 | — | — | 0.38 ± 0.02 | — | — |
| Vmax (min−1) | — | 11 ± 1 | <0.1 | — | 2.8 ± 0.3 | <0.1 |
| Vmax/Km (μl/min per mg) | 3.5 | — | — | 7.2 | — | — |
| Vmax/Km (μl/min per nmol) | — | 150 | N.A. | — | 8.5 | N.A. |
N.A., not available; —, not calculated.