Kinetic parameters for JWH-018 oxidation
Km and Vmax values are given in micromolar concentrations and picomoles per minute per nanomole of protein for recombinant P450 isoforms and picomoles per minute per milligram of protein for HLM, respectively. Vmax values represent the highest activity measured before inhibition is seen, and Km values represent the lowest concentration of substrate that results in an activity of 1/2 “observed” Vmax.
| JWH-018 Metabolites | JWH-018 ω-OH | JWH-018 ω-COOH | JWH-018 ω-1-OH |
|---|---|---|---|
| CYP1A2 | |||
| Vmax | 833 ± 25 | 53 ± 9.4 | 1438 ± 32 |
| Km | 5.3 ± 0.74 | 2.3 ± 0.80 | 4.7 ± 0.49 |
| Kinetic fit | M-M | SI | M-M |
| CYP2C9 | |||
| Vmax | 835 ± 19 | N.D. | 487 ± 14 |
| Km | 0.81 ± 0.07 | N.D. | 1.3 ± 0.13 |
| Kinetic fit | Hill, n = 2.2 | N.D. | Hill, n = 2.0 |
| CYP2C19 | |||
| Vmax | 535 | 13,161 | 5157 |
| Km | 82 | 36,648 | 106 |
| Kinetic fit | —a | — | — |
| CYP2D6 | |||
| Vmax | 26 ± 1.0 | N.D. | 43 ± 2.0 |
| Km | 2.8 ± 0.52 | N.D. | 3.2 ± 0.70 |
| Kinetic fit | M-M | N.D. | M-M |
| HLM | |||
| Vmax | 3.9 ± 0.25 | N.D. | 15.1 ± 1.5 |
| Km | 7.8 ± 1.9 | N.D. | 26.3 ± 7.7 |
| Kinetic fit | M-M | N.D. | M-M |
M-M, Michaelis-Menten; SI, competitive substrate inhibition; N.D., not detected.
↵a —, the kinetic model did not fit the classic Hill equation for activation kinetics.