Steroid hydroxylation by human fetal CYP3A7 and human NADPH-cytochrome P450 reductase coexpressed in insect cells using baculovirus.
Article Details
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Ohmori S, Fujiki N, Nakasa H, Nakamura H, Ishii I, Itahashi K, Kitada M
Steroid hydroxylation by human fetal CYP3A7 and human NADPH-cytochrome P450 reductase coexpressed in insect cells using baculovirus.
Res Commun Mol Pathol Pharmacol. 1998 Apr;100(1):15-28.
- PubMed ID
- 9644715 [ View in PubMed]
- Abstract
Human fetal CYP3A7 and human NADPH-cytochrome P450 reductase were coexpressed in insect cells, TN-5, infected with a recombinant baculovirus carrying both cDNAs. The expression of reductase in TN-5 cells was shown to be sufficient for the CYP3A7 dependent 16 alpha-hydroxylation of dehydroepiandrosterone. However, the extra addition of cytochrome b5 and phospholipid was necessary to obtain a maximal activity of CYP3A7 catalyzing the reaction. CYP3A7 expressed in TN-5 cells was capable of metabolizing testosterone, cortisol and dehydroepiandrosterone 3-sulfate as well as dehydroepiandrosterone. The apparent Vmax for 6 beta-hydroxylations of testosterone was similar to that obtained for 6 beta-hydroxylation of cortisol (2.9 versus 2.5 nmol/nmolP450/min). In contrast, the apparent Vmax for 16 alpha-hydroxylation of dehydroepiandrosterone and its 3-sulfate were 20 and 2 times greater than those observed for steroid 6 beta-hydroxylations, respectively (67.5 and 5.8 versus 2.5-2.9 nmol/nmol P450/min). On the other hand, the apparent K(m) for 6 beta-hydroxylations of testosterone and cortisol were greater than those for 16 alpha-hydroxylations (120 and 860 versus 46-58 microM). Thus, CYP3A7 was active for steroid 6 beta-hydroxylations and 16 alpha-hydroxylations, but there were greater differences in Vmax/K(m) ratios between these reactions.
DrugBank Data that Cites this Article
- Drug Enzymes
Drug Enzyme Kind Organism Pharmacological Action Actions Testosterone Cytochrome P450 3A7 Protein Humans UnknownSubstrateDetails Testosterone cypionate Cytochrome P450 3A7 Protein Humans UnknownSubstrateDetails Testosterone enanthate Cytochrome P450 3A7 Protein Humans UnknownSubstrateDetails Testosterone undecanoate Cytochrome P450 3A7 Protein Humans UnknownSubstrateDetails