Kinetic parameters for the formation of NNK metabolites by mouse lung and liver microsomes
Apparent Km and Vmax values for the microsomal formation of three major NNK metabolites (HPB, NNK-N-oxide, and sodium bisulfite-trapped OPB) were determined as described under Materials and Methods. Values represent means ± S.D. of values determined for three separate microsomal samples, each prepared from tissues pooled from five 2-month-old female mice.
| Metabolite | Strain | Lung | Liver | ||||
|---|---|---|---|---|---|---|---|
| Km | Vmax | Vmax/Km | Km | Vmax | Vmax/Km | ||
| μM | pmol/min/mg | μM | pmol/min/mg | ||||
| OPB | WT (B6) | 28.0 ± 1.9 | 57.3 ± 1.8 | 2.0 | 29 ± 4 | 220 ± 10 | 7.6 |
| Cyp2a5-null | 40.2 ± 2.1a | 61.5 ± 2.0 | 1.5 | 55 ± 5a | 210 ± 10 | 4.0 | |
| HPB | WT (B6) | 2.8 ± 0.3 | 24.3 ± 0.5 | 8.7 | 18 ± 3 | 105 ± 5 | 5.9 |
| Cyp2a5-null | 2.9 ± 0.3 | 24.4 ± 1.0 | 8.4 | 65 ± 15a | 70 ± 8a | 1.1 | |
| NNK-N-oxide | WT (B6) | 1.6 ± 0.2 | 35.8 ± 3.1 | 22.4 | 84 ± 18 | 19 ± 2 | 0.2 |
| Cyp2a5-null | 1.9 ± 0.3 | 38.7 ± 2.2 | 20.4 | 83 ± 16 | 20 ± 2 | 0.2 | |
↵a p < 0.01, compared with WT mice, Student's t test.