Kinetic analysis of UGTs-induced O-glucuronidation of trans- and cis-4-OH-TAM
All data are the mean ± S.D. based on three independent experiments. Homogenates from cells overexpressing UGTs 1A6, 2B4, 2B10, or 2B11 exhibited no detectable glucuronidating activity against 4-OH-TAM.
UGT | trans-4-OH-TAM | cis-4-OH-TAM | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Vmax | KM | Vmax/KM | Vmax | KM | Vmax/KM | |||||
| pmol·min−1·μg−1 | μM | μl·min−1·μg−1 | pmol·min−1·μg−1 | μM | μl·min−1·μg−1 | |||||
| 1A1 | 3.4 ± 0.2 | 124 ± 16 | 0.028 ± 0.004 | 24.6 ± 3.5 | 193 ± 26 | 0.13 ± 0.017 | ||||
| 1A3 | 1.9 ± 0.3 | 93.7 ± 17.7 | 0.020 ± 0.001 | 6.0 ± 0.5 | 165 ± 26 | 0.036 ± 0.008 | ||||
| 1A7 | 1.2 ± 0.2 | 166 ± 27 | 0.0074 ± 0.0002 | 0.20 ± 0.03 | 7.4 ± 1.3 | 0.027 ± 0.001 | ||||
| 1A8 | 3.2 ± 0.2 | 22.7 ± 2.4 | 0.14 ± 0.02 | 4.9 ± 0.2 | 56.1 ± 9.1 | 0.088 ± 0.011 | ||||
| 1A9 | 3.0 ± 0.1 | 319 ± 38 | 0.009 ± 0.001 | 4.9 ± 1.1 | 69.9 ± 19.3 | 0.071 ± 0.005 | ||||
| 1A10 | 4.7 ± 0.3 | 96.1 ± 7.7 | 0.049 ± 0.006 | 35.3 ± 0.2 | 30.0 ± 5.1 | 1.20 ± 0.20 | ||||
| 2B7 | 0.55 ± 0.18 | 3.7 ± 0.6 | 0.15 ± 0.03 | 1.8 ± 0.6 | 14.8 ± 4.5 | 0.12 ± 0.02 | ||||
| 2B15 | N.D. | 1.6 ± 0.2 | 19.6 ± 1.1 | 0.08 ± 0.01 | ||||||
| 2B17 | 0.017 ± 0.001 | 40.6 ± 6.2 | 0.001 ± 0.0001 | 0.21 ± 0.02 | 18.0 ± 2.1 | 0.012 ± 0.001 | ||||
N.D., not detectable.