Table 2.
Preliminary analysis of kinetic mechanism describing R- and S-7-hydroxywarfarin glucuronidationa
| Substrate | Metabolitesb | Model | Model Preference | Parameters for Preferred Model | ||
|---|---|---|---|---|---|---|
| Vmax1c | Km (μM) | Ki (μM) | ||||
| R-7-HOWAR | 7-HOWAR-4-GLUC | Substrate Inhibition | 70.7 % | 35.4 (30.4–40.4) | 60.8 (36.9–84.8) | 2640 (1360–3920) |
| 7-HOWAR-7-GLUC | Michaelis-Menten | 75.2 % | 1090 (1040–1140) | 122 (100–145) | - | |
| S-7-OHWAR | 7-HOWAR-4-GLUC | Substrate Inhibition | >99.99 % | 19.7 (17.19–22.2) | 111 (77.7–145) | 2840 (1650–4030) |
| 7-HOWAR-7-GLUC | Substrate Inhibition | 99.7 % | 1470 (790–2150) | 929 (362–1500) | 1310 (259–2370) | |
The nonsymmetrical 95 % confidence intervals for parameters are shown in parentheses.
Glucuronidation resulted in conjugation of the hydroxyl group at either the C4 or C7 position resulting in the formation of 7-HOWAR-4-GLUC or 7-HOWAR-7-GLUC, respectively, as described in the Discussion.
Units are nmol/min/mg protein