Table 1.
Thalidomide hydroxylation catalyzed by human or monkey liver microsomes, recombinant human or monkey P450s expressed in E. coli membranes, and purified human P450s in reconstituted systems.
| product | |||||
|---|---|---|---|---|---|
| enzyme source | P450 | (R)-thalidomide | (S)-thalidomide | ||
| 5-hydroxythalidomide | 5’-hydroxythalidomide | 5-hydroxythalidomide | 5’-hydroxythalidomide | ||
| pmol formed min−1 (mg protein)−1 | |||||
| human liver microsomes | 0.08 | 0.59 | 0.03 | < 0.01 | |
| monkey liver microsomes | 0.21 | 2.28 | 0.07 | 0.18 | |
| pmol min−1 (nmol P450)−1 | |||||
| E. coli membranes | 3A4 | 2.0 | < 0.1 | < 0.1 | < 0.1 |
| human | 3A5 | 2.3 | < 0.1 | < 0.1 | < 0.1 |
| 3A7 | 2.8 | < 0.1 | < 0.1 | < 0.1 | |
| monkey | 3A8 | 12 | < 0.1 | 3.4 | < 0.1 |
| 3A5 | 9.2 | < 0.1 | 2.9 | < 0.1 | |
| reconstituted system | 2C19 | 2.4 | 1.7 | 1.1 | < 0.1 |
| human | 3A4 | 2.0 | < 0.1 | 0.9 | < 0.1 |
| 3A5 | 2.5 | < 0.1 | 0.7 | < 0.1 | |
Thalidomide (1000 µM) was incubated with liver microsomes (1.0 mg protein mL−1) or P450 2C19, 3A4, 3A5, 3A7, and 3A8 (100 nM P450) at 37 °C for 60 min. Results are presented as means of results of duplicate determination.