P450 Form | Rate of 2-Hydroxylation of EE | ||||||||
---|---|---|---|---|---|---|---|---|---|
pmol P450/mg proteina | pmol/min/pmol rP450 | pmol/min/mgb | %TNRc | %1d | |||||
CYP1A1 | NAe | 0.246 | NDf | NDf | NDf | ||||
CYP1A2 | 8.9 | 0.013 | 0.1 | 2.4 | 6.0 | ||||
CYP2C8 | NDf | 0.008 | NDf | NDf | 26 | ||||
CYP2C9 | 44 | 0.025 | 1.1 | 23 | 24 | ||||
CYP2C19 | 19 | 0.021 | 0.4 | 8.0 | NDf | ||||
CYP3A4 | 22 | 0.134 | 2.9 | 61 | 52 | ||||
CYP3A5 | 4.1 | 0.068 | 0.3 | 5.8 | NDf | ||||
TNR |
|
| 4.8 |
|
|
↵ a The abundance of cytochrome P450 protein in native human liver microsomes was quantified by Western blot with P450 isozyme-specific polyclonal antibody
↵ b Rate was normalized using the specific content of each P450 isozyme in native human liver microsomes (Table 1). For example, the normalized rate for CYP3A4 = rate produced by rCYP3A4 (0.134 pmol/min/pmol rP450) × CYP3A4 content in liver microsomes (22 pmol/mg protein) = 2.9 pmol/min/mg
↵ c Data expressed as percentage of TNR, where TNR = 4.8 pmol/min/mg
↵ d Inhibition of 2-hydroxylation of [3H]EE (5 μM) by isozyme-specific monoclonal antibodies (5 μl) in a pool (n = 7) of female human liver microsomes
↵ e NA, not applicable
↵ f ND, not determined since no isozyme-specific antibodies were available for the inhibition study or the immunoblotting assays