Investigations on the role of cytochrome b5 and divalent cations in the maximal nifedipine oxidase activity of human liver.
Native human cytochrome P4503A4 was most active in nifedipine oxidation when incorporated into a binary phospholipid vesicular system with human NADPH-cytochrome P450 reductase. The turnover numbers were estimated to be 17.6 and 19.6 min-1 in the presence of Mg2+ or Ca2+ ions (5 mmol/l) in the test system, respectively. Inclusion of b5 in the vesicular CYP3A4: reductase system results in a slightly lower nifedipine oxidase activity of 16.9 min-1 in the presence of Mg2+ ions. These results demonstrate that b5 is not an essential component in CYP3A4 catalyzed nifedipine oxidation in human liver.
Müller-Enoch
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Department of Physiological Chemistry, Universität of Ulm, Germany.
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002413:Cations, Divalent / Q000494:pharmacology*; D020355:Cholates / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D051544:Cytochrome P-450 CYP3A; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D015786:Cytochromes b5 / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008274:Magnesium / Q000378:metabolism / Q000494:pharmacology; D006899:Mixed Function Oxygenases / Q000378:metabolism*; D008969:Molecular Sequence Data; D009251:NADPH-Ferrihemoprotein Reductase / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism; D011817:Rabbits; D051381:Rats
D002413:Cations, Divalent; D020355:Cholates; D010743:Phospholipids; D015786:Cytochromes b5; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; C104464:CYP3A protein, human; D051544:Cytochrome P-450 CYP3A; C510163:CYP3A4 protein, human; D009251:NADPH-Ferrihemoprotein Reductase; D005978:Glutathione; D008274:Magnesium; D002118:Calcium