TABLE 3.
Kinetic parameters of methamphetamine and metabolites determined from modeling the data in Fig. 4 and Supplemental Fig. 4
Models were chosen based on examination of Eadie-Hofstee plots. Methamphetamine was fit to a standard Michaelis-Menten equation. Amphetamine uptake kinetics was fit to a biphasic Michaelis-Menten equation (eq. 5). p-OHMA hOCT1- and hOCT3-mediated transport were fit to a standard Michaelis-Menten equation. Sigmoidal kinetics of hOCT2-mediated p-OHMA transport was obtained by fitting transporter-mediated uptake to the Michaelis-Menten equation with a Hill slope (eq. 5) for the substrate concentration and half-maximal transport concentration (K1/2 in place of Km). Results represent mean ± S.D. of three independent experiments each run in triplicate.
| Compound |
Transporter |
Km1 |
Vmax1 |
Km2 |
Vmax2 |
|---|---|---|---|---|---|
| μM | pmol/mg/min | μM | pmol/mg/min | ||
| Methamphetamine | hOCT2 | 2.09 ± 0.88 | 49.7 ± 12.2 | ND | ND |
| Amphetamine | hOCT2 | 0.830 ± 0.55 | 34.6 ± 23.7 | 534 ± 350 | 853 ± 474 |
| p-OHMA | hOCT1 | 14.5 ± 8.7 | 312 ± 163 | NA | NA |
| hOCT2 | K1/2: 31.8 ± 9.3; H: 1.64 ± 0.15 | 1780 ± 718 | NA | NA | |
| hOCT3 | 53.3 ± 6.2 | 1290 ± 830 | NA | NA |
NA, not applicable; ND, not determined (due to high diffusion).