TABLE 1

Effect of cytochrome b5 upon ifosfamide N-dechloroethylation (pmol of 2-DCEI and 3-DCEI formed/min/pmol P450) by cDNA-expressed CYP3A4 and CYP3A5


P450

3A4

3A5

3A4

3A5

3A4

3A5
Cytochrome b5 None Added (1:3 ratio)a Coexpressedb
2-DCEI formation 0.059 0.046 0.024 0.077 0.378 0.068
3-DCEI formation 0.283 0.676 0.296 0.938 5.05 2.25
2- and 3-DCEI formation
0.342
0.722
0.320
1.02
5.43
2.32
  • a Molar ratio of P450 to cytochrome b5; cytochrome c reductase activity [nmol/(min × mg protein)] of 370 and 2200 for CYP3A4 and CYP3A5, respectively.

  • b Coexpressed cytochrome c reductase activity [nmol/(min × mg protein)] at 5100 and 3900, and cytochrome b5 (pmol/mg protein) content at 1400 and 1600 for CYP3A4 and CYP3A5, respectively.