Table 2.
Comparison of the activities of POR variants in various assays
| Drug Metabolism | Steroidogenesis | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| CYP | 3A4 | 1A2 | 2C19 | 17 | 19 | |||||
| Reaction | 6β-OH T | 1-OH M | 4-OH M | 3-OH Q | N- deMe E | EOMCC | EOMCC | 17α-OH | 17, 20 lyase | aromatase |
| WT | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 | 100 |
| Q153R | 129 | 94 | 92 | 150 | 76 | 144 | 284 | 31 | 27 | ND |
| A287P | 17 | 17 | 14 | 3 | nil | nil | nil | 40 | 21 | 104 |
| R457H | nil | nil | nil | 1 | nil | nil | nil | 3 | nil | 1 |
| A503V | 77 | 61 | 74 | 89 | 97 | 85 | 113 | 68 | 58 | ND |
All data are Vmax/Km, shown as a percentage of the wild-type control, set at 100%; ND, not done. The reactions assayed are: 6β-hydroxylation of testosterone (6β-OH T), 1-hydroxylation (1-OH M) and 4-hydroxylation (4-OH M) of midazolam, 3-hydroxylation of quinidine (3-OH Q), and N-demethylation of erythromycin (N-deMe E) by CYP3A4 (Table 1–4 of this work); activation of fluorogenic EOMCC by CYP1A2 and CYP2C19 (from [30]); 17α-hydroxylation of progesterone (17α OH) and 17,20 lyase cleavage of 17OH-pregnenolone by CYP17 (from [19]); aromatization of androstenedione to estrone by CYP19 (from [41]).