TABLE 3.
Effect of co-incorporation of CYP3A4, CYP3A5, and CYP2E1 on CYP3A-dependent 7-BQ O-debenzylation in model microsomal systems
The values given in the table were obtained by averaging the results of 2–5 individual measurements (each with a different preparation of model microsomes), and the ± values show the confidence interval calculated for p = 0.05.
| Systema | S50 | nHb | Vmax | kcatc | RANFd |
|---|---|---|---|---|---|
| μm | mol · mol(3A) · min−1 | min−1 | |||
| SS(R)3A4 | |||||
| −ANF | 46 ± 11 | 2.05 ± 0.49 | 0.86 ± 0.65 | 2.9 ± 0.8 | 1.7 ± 0.2 (0.02) |
| +ANF | 72 ± 22 | 1.57 ± 0.72 | 2.0 ± 1.2 | 4.8 ± 1.0 | |
| SS(R)3A5 | |||||
| −ANF | 76 ± 39 | 2.32 ± 0.65 | 1.1 ± 0.9 | 5.4 ± 3.0 (0.09) | 0.92 ± 0.1 (0.91) |
| +ANF | 62 ± 37 | 2.70 ± 0.63 | 1.3 ± 0.9 | 5.1 ± 2.3 (0.78) | |
| SS(R)3A4/3A5 | |||||
| −ANF | 61 ± 37 | 2.07 ± 0.54 | 3.1 ± 2.6 | 8.6 ± 0.1 (<0.01) | 0.85 ± 0.5 (0.62) |
| +ANF | 46 ± 11 | 2.00 ± 0.74 | 2.2 ± 0.7 | 7.3 ± 4.4 (0.18) | |
| SS(R)3A4/2E1 | |||||
| −ANF | 62 ± 34 | 1.48 ± 0.30 | 0.40 ± 0.21 | 2.2 ± 1.6 (0.64) | 2.0 ± 1.0 (0.35) |
| +ANF | 51 ± 6 | 2.31 ± 1.39 | 0.68 ± 0.10 | 3.2 ± 1.5 (0.06) | |
| SS(R)3A5/2E1 | |||||
| −ANF | 87 ± 33 | 2.26 ± 1.03 | 0.64 ± 0.24 | 2.2 ± 1.6 (0.37) | 1.8 ± 0.6 (0.44) |
| +ANF | 82 ± 49 | 2.80 ± 1.16 | 0.76 ± 0.80 | 3.7 ± 1.7 (0.45) | |
a Shown in the absence and in the presence of 25 μm ANF.
b The data were fitted with the Hill equation, and nH represents the Hill coefficient.
c Turnover rate calculated per concentration of CPR. The values in parentheses represent the p values of Student's t test for the hypothesis of equality of the respective values of kcat with the value observed for SS(R)3A4. The p values ≤0.05 are underlined to emphasize the effects with high statistical significance.
d Relative effect of the addition of 25 μm ANF on Vmax. The values represent the averages of the ratios of Vmax values obtained in the presence and in the absence of ANF with the same preparation of model microsomes. The values in parentheses represent the p values of Student's t test for the hypothesis that the respective RANF ratios are equal to unity (i.e. that ANF has no effect on the enzyme turnover). The p values ≤0.05 are underlined to emphasize the effects with high statistical significance.