Kinetic parameters for losartan oxidation activities of wild-type and variant CYP2C9s
Data are presented as the mean ± S.D. of three to four different expression experiments.
Recombinant Enzymes (Amino Acid Alteration) | Km | Vmax | Clearance (Vmax/Km) |
|---|---|---|---|
| μM | pmol/min/nmol P450 | μl/min/nmol P450 | |
| CYP2C9.1 (wild type) | 1.12 ± 0.13 | 780 ± 82 | 704 ± 77 |
| CYP2C9.3 (I359L) | 0.99 ± 0.10 | 157 ± 30*** | 161 ± 42*** |
| CYP2C9.13 (L90P) | 2.76 ± 0.64*** | 47.0 ± 2.3*** | 17.6 ± 3.6*** |
| CYP2C9.26 (T130R) | 1.50 ± 0.13 | 40.3 ± 6.2*** | 26.8 ± 2.0*** |
| CYP2C9.28 (Q214L) | 2.03 ± 0.42*** | 180 ± 18*** | 90.2 ± 11.7*** |
| CYP2C9.30 (A477T) | 0.77 ± 0.12 | 4.7 ± 0.4*** | 6.3 ± 1.3*** |
| CYP2C9.33 (R132Q) | 1.03 ± 0.21 | 7.3 ± 0.3*** | 7.3 ± 1.4*** |
| CYP2C9.34 (R335Q) | 1.06 ± 0.11 | 550 ± 27*** | 526 ± 75*** |
| BD Gentest CYP2C9.1 | 1.34 | 630 | 470 |
| BD Gentest human liver microsome | 2.85 | 48.2 | 16.9 |
↵*** P < 0.001 vs. wild type. One-way ANOVA with a post hoc Dunnett multiple comparisons test.