TABLE 1.
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.