TABLE 1.
Kinetic parameters of EROD and MROD inhibition by quinidine in microsomes
| Microsomes Origin | Ks1 ± S.E. | Ks2 ± S.E. | Ki ± S.E. | α | Quinidine Inhibition Type |
|---|---|---|---|---|---|
| μM | μM | μM | |||
| EROD | |||||
| rCYP1A1 | 0.09 ± 0.008 | 11 ± 1 | 3.3 ± 0.35 | 31 ± 8 | Mixed |
| rCYP1A2 | (Km) 1.2 ± 0.2 | NA | NA | NA | NA |
| Cyp1a KO | 0.83 ± 0.04 | 13 ± 1.5 | 422 ± 18 | NA | Noncompetitive |
| MROD | |||||
| rCYP1A1 | 0.47 ± 0.07 | 1.3 ± 0.18 | 2.2 ± 0.18 | NA | Competitive |
| rCYP1A2 | 0.58 ± 0.08 | 12 ± 3.5 | NA | NA | NA |
| Cyp1a KO | 0.96 ± 0.18 | 3.4 ± 0.8 | 272 ± 28 | NA | Noncompetitive |
Ki, dissociation constant of the enzyme-inhibitor complex; Ks1, dissociation constant of the productive enzyme-substrate complex; Ks2, dissociation constant of the inhibitory enzyme-substrate complex; NA, not applicable; rCYP1A1, recombinant CYP1A1; rCYP1A2, recombinant CYP1A2; α, parameter describing the effect of inhibitor binding on the binding of the substrate and vice versa.