Glucurnidation of amines catalyzed by expressed human UGT1A3
| Substrate | Glucuronide Formation |
|---|---|
| pmol/min/mg of protein | |
| Primary amines | |
| α-Naphthylamine | 12 ± 2 |
| β-Naphthylamine | 15 ± 3 |
| 2-Aminobiphenyl | 11 ± 1 |
| 4-Aminobiphenyl | 77 ± 9 |
| 2-Aminofluorene | 84 |
| Benzidine | 5 |
| Secondary amines | |
| Diphenylamine | 12 ± 4 |
| Desipramine | ND1-a |
| Nortriptyline | ND |
| Desmethylclozapine | ND |
| Tertiary amines | |
| Imipramine | 6 ± 1 |
| Amitriptyline | 38 ± 5 |
| Cyproheptadine | 87 ± 10 |
| Tripelennamine | 5 |
| Doxepin | 7 |
| Chlorpromazine | 3 |
| Ketotifen | 11 |
| Clozapine | 6 |
| Loxepine | 7 |
| Diphenhydramine | 2 |
| Promethazine | 2 |
| Trifluoperazine | ND |
| Pyrilamine | ND |
| Cyclizine | ND |
| Carbamazepine | ND |
Assays were performed at pH 8.4 and 37°C for 2.0 hr, using whole-cell homogenates of HK293 cells expressing UGT1A3. The concentration of UDP-glucuronic acid was 2.0 mM, and the aglycone concentrations were 0.5 mM. Enzymatic rates are expressed as the mean ± SD of determinations from three different transfections or the average determinations from two transfections.
↵1-a ND, glucuronide formation was not detected (limits of detection, 2.0 pmol/min/mg of protein).