Effects of enzyme sources on midazolam 1'-hydroxylation activity catalyzed by recombinant cytochrome P450 3A4 in combination with NADPH-cytochrome P450 reductase.
The influence of the enzyme source such as phospholipid and expression ratio of NADPH-cytochrome P450 reductase on midazolam 1'-hydroxylation activity of cytochrome P450 3A4 was investigated in reconstituted systems and in membranes using bicistronic expressions. Preferable ratio of P450 reductase over human P450 3A4 would be a determinant factor for the drug metabolism studies.
Emoto
Chie
C
Laboratory of Drug Metabolism and Pharmacokinetics, Showa Pharmaceutical University, Machida, Tokyo 194-8583, Japan.
Murayama
Norie
N
Yamazaki
Hiroshi
H
D002462:Cell Membrane / Q000201:enzymology; D051544:Cytochrome P-450 CYP3A / Q000235:genetics / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D004926:Escherichia coli / Q000201:enzymology; D015870:Gene Expression; D006801:Humans; D006900:Hydroxylation; D008874:Midazolam / Q000378:metabolism*; D009251:NADPH-Ferrihemoprotein Reductase / Q000235:genetics / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*
D018076:DNA, Complementary; D010743:Phospholipids; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D009251:NADPH-Ferrihemoprotein Reductase; D008874:Midazolam