Table 2.
Effect of testosterone on the progesterone 6β-hydroxylase activities of P450 3A4 wild-type and the site-directed mutant L211F/D214E
| Substrate [[14C]Pro], μM | P450 3A4 [Test], μM
|
L211F/D214E [Test], μM
|
||||
|---|---|---|---|---|---|---|
| 0 | 25 | 100 | 0 | 25 | 100 | |
| 5 | 0.9* | 1.4 (149) | 1.7 (189) | 2.2 | 2.0 (91) | 1.6 (73) |
| 10 | 2.1 | 2.7 (129) | 3.1 (148) | 4.3 | 4.0 (93) | 2.9 (67) |
| 25 | 5.7 | 6.4 (112) | 6.9 (121) | 8.9 | 8.3 (93) | 5.9 (66) |
| 50 | 10.9 | 12.4 (114) | 11.5 (106) | 13.4 | 13.6 (101) | 10.7 (80) |
*
Values are expressed as nanomoles of 6β-OH progesterone formed per minute per nanomole of P450 and are the average of duplicate determinations. Numbers in parentheses represent the rate of 6β-OH progesterone formation as a percentage of the rate of product formation in the absence of added testosterone.