Rates of in vitro metabolism of nicotine by liver microsomes from WT and Cyp2a5-null mice
Cotinine formation was determined as described under Materials and Methods. Reaction mixtures contained 50 mM potassium phosphate buffer, pH 7.4, 1.0 or 10 μM nicotine, 0.5 mg/ml liver microsomal protein, and 1.0 mg/ml liver cytosol protein (as a source of aldehyde oxidase) from 2-month-old male mice, and 1.0 mM NADPH. The values presented are means ± S.D. (n = 3).
Nicotine Concentration
Strain
Rates of Cotinine Formation
Ratio of Null/WT
pmol/min/mg
1.0 μM
WT
39.1 ± 1.2
0.15
Cyp2a5-null
5.7 ± 0.8*
10 μM
WT
221 ± 2
0.27
Cyp2a5-null
58.6 ± 3.8*
↵* , P < 0.01, compared with the corresponding WT value.