Selectivity of probe substrate catalysis by the five major human hepatic CYPs
Probe Reaction | Substrate Concentration | V | ||||
---|---|---|---|---|---|---|
CYP1A2 | CYP2C9 | CYP2C19 | CYP2D6 | CYP3A4 | ||
pmol · min−1 · pmol−1 | ||||||
EROD | 3 | 0.40 | 0.01 | 0.05 | ND | ND |
1 | 0.30 | ND | ND | ND | ND | |
NaproxenO-demethylation | 2000 | 3.90 | 6.80 | 4.80 | 0.08 | ND |
300 | 3.46 | 2.36 | 0.87 | ND | ND | |
DiazepamN-demethylation | 100 | ND | 0.03 | 2.61 | ND | 1.43 |
20 | ND | 0.02 | 1.47 | ND | 0.48 | |
DextromethorphanO-demethylation | 30 | ND | 0.67 | 1.81 | 4.00 | 0.04 |
3 | ND | 0.03 | 0.21 | 2.90 | ND | |
ErythromycinN-demethylation | 300 | ND | 0.09 | 0.23 | 0.31 | 2.59 |
40 | ND | ND | 0.03 | 0.03 | 1.62 |
ND not detectable (< 0.005 min−1).
Enzyme sources were E. coli membranes expressing CYP1A2, CYP2C9, CYP2C19 (single plasmid), CYP2D6, and CYP3A4 as described inMaterials and Methods.