Kinetic parameters for amitriptyline, imipramine, and diphenhydramine N-glucuronidation by recombinant His-tagged UGT1A3, UGT1A4, and UGT2B10
| Km or S50 | Vmax | Normalized Vmax | CLint or CLmax | Ki | n | Kinetic Model | |
|---|---|---|---|---|---|---|---|
| µM | pmol/min/mg | pmol/min/mg | nl/min/mg | µM | |||
| Amitriptyline | |||||||
| UGT1A3 | 490 ± 42 | 740 ± 71 | 22 ± 2.1 | 23 ± 3.8 | 2.3 ± 0.4 | Hill | |
| UGT1A4 | 450 ± 72 | 530 ± 120 | 56 ± 13 | 130 ± 370 | Michaelis-Menten | ||
| UGT2B10 | 7.5 ± 5.1 | 7.5 ± 2.0 | 7.5 ± 2.0 | 1600 ± 1500 | 130 ± 28 | Substrate inhibition | |
| Imipramine | |||||||
| UGT1A3 | 760 ± 110 | 24 ± 5.6 | 0.7 ± 0.2 | 0.6 ± 0.1 | 1.2 ± 0.0 | Hill | |
| UGT1A4 | 500 ± 55 | 55 ± 2.1 | 5.8 ± 0.2 | 8.2 ± 0.7 | 1.1 ± 0.0 | Hill | |
| UGT2B10 | 7.2 ± 5.5 | 2.5 ± 0.3 | 2.5 ± 0.3 | 470 ± 260 | 380 ± 250 | Substrate inhibition | |
| Diphenhydramine | |||||||
| UGT1A3 | N.A. | N.A. | N.A. | N.A. | N.A | ||
| UGT1A4 | 470 ± 26 | 150 ± 8.2 | 16 ± 0.9 | 34 ± 1.4 | Michaelis-Menten | ||
| UGT2B10 | 37 ± 13 | 3.6 ± 1.0 | 3.6 ± 1.0 | 99 ± 8.7 | Michaelis-Menten |
CLint, intrinsic clearance; CLmax, maximum clearance; N.A., not applicable.