Article Figures & Data
Figures
- Fig. 1.
Primary oxidative metabolites of methoxychlor formed by human liver P450s.
- Fig. 2.
Effect of various molar ratios of CYP2C9 and CYP2C19 to CPR on the metabolic activity of reconstituted systems. See Materials and Methods for incubation conditions. Values represent the mean ± S.E. of at least three determinations. *, statistically significant (p < 0.05) difference between the enzymatic activities (compared with the enzymatic activity measured at a P450/CPR ratio of 1:1). A, methoxychlor-O-demethylation by CYP2C9 (125 nM CYP2C9 per incubation). B, methoxychlor-O-demethylation by CYP2C19 (25 nM CYP2C19 per incubation). C, diclofenac 4′-hydroxylation by CYP2C9 (50 nM CYP2C9 per incubation). D, S-mephenytoin 4′-hydroxylation by CYP2C19 (50 nM CYP2C19 per incubation).
- Fig. 3.
Effect of CYP2C9 on CYP2C19-mediated metabolism of methoxychlor and S-mephenytoin as a function of NADPH-CPR concentration. A, methoxychlor-O-demethylation. Methoxychlor-O-demethylation was determined in both single (CYP2C9 or CYP2C19) and binary (CYP2C9 + CYP2C19) reconstituted systems. The concentration of CYP2C9 was 125 nM; the concentration of CYP2C19 was 25 nM. B, S-mephenytoin 4′-hydroxylation. S-Mephenytoin 4′-hydroxylation was determined in single (CYP2C19) and binary (CYP2C9 and CYP2C19) reconstituted systems. The concentration of CYP2C9 was 250 nM; the concentration of CYP2C19 was 50 nM.
- Fig. 4.
The effect of CYP2C9 on CYP2C19-dependent methoxychlor metabolism. Values represent the mean ± S.E. of at least three determinations. See Materials and Methods for incubation conditions. A, effects at a CYP2C19/CPR ratio of 2:1. B, effects at a CYP2C19/CPR ratio of 1:2. The amount of CYP2C19 added was 25 pmol/1 ml of incubation (i.e., 25 nM).
- Fig. 5.
Effect of CYP2C19 on CYP2C9-dependent diclofenac 4′-hydroxylation. Values represent the mean ± S.E. of at least three determinations. Effects at a CYP2C9/CPR ratio of 1:3. See Materials and Methods for incubation conditions. The amount of CYP2C9 added was 25 pmol/0.5 ml of incubation (i.e., 50 nM).
