Formation of catechol products from 4-OH-tam and 3-OH-tam (Droloxifene) catalyzed by human liver microsomes
| Donor # | Liver Microsomes | Substrate | Methylated Catechol | |
|---|---|---|---|---|
| CYP3A Activity 3-a | CYP2D6 Activity 3-b | |||
| nmol/mg protein | ||||
| 166 | 7.0 | 763 | 4-OH-tam | 3.16 ± 0.04 |
| 51 | 6.2 | 507 | 4-OH-tam | 1.42 ± 0.09 |
| 225 | 8.0 | 261 | 4-OH-tam | 3.15 ± 0.60 |
| 59 | 10.0 | 234 | 4-OH-tam | 1.62 ± 0.13 |
| 80 | 1.5 | 856 | 4-OH-tam | 1.67 ± 0.11 |
| 57 | 0.3 | 568 | 4-OH-tam | 0.37 ± 0.18 |
| 56 | 2.0 | 181 | 4-OH-tam | 0.71 ± 0.12 |
| 185 | 2.3 | 180 | 4-OH-tam | 0.99 ± 0.12 |
| 94 | 3.4 | 186 | 4-OH-tam | 0.60 ± 0.25 |
| 80 | 1.5 | 856 | 3-OH-tam | 8.63 ± 0.34 |
| 225 | 8.0 | 261 | 3-OH-tam | 8.22 ± 0.72 |
Human liver microsomes (50 μg), 3-OH-tam, or 4-OH-tam (25 μM), DTT (50 μM), COMT (100 U), SAM (200 μM/1μCi), and NADPH-regenerating system were incubated in a final volume of 0.4 ml for 30 min at 37°C. Values represent a mean ± S.D. of triplicate measurements.
↵3-a Catalytic activity (mean ± S.D.) of 135 human livers = 2.5 ± 2.1 nmol 6β-hydroxy-testosterone/mg protein/min.
↵3-b Catalytic activity (mean ± S.D.) of 135 human livers = 273.6 ± 179.8 pmol dextromethorphan-O-demethylation/mg protein/min).