Abstract
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.
MeSH terms
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Amino Acid Sequence
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Animals
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Calcium / pharmacology
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Cations, Divalent / pharmacology*
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Cholates / metabolism
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Chromatography, High Pressure Liquid
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Cytochrome P-450 CYP3A
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Cytochrome P-450 Enzyme System / metabolism*
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Cytochromes b5 / metabolism*
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Glutathione / metabolism
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Humans
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In Vitro Techniques
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Liver / drug effects
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Liver / enzymology*
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Magnesium / metabolism
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Magnesium / pharmacology
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Mixed Function Oxygenases / metabolism*
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Molecular Sequence Data
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NADPH-Ferrihemoprotein Reductase / metabolism
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Phospholipids / metabolism
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Rabbits
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Rats
Substances
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Cations, Divalent
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Cholates
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Phospholipids
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Cytochromes b5
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Cytochrome P-450 Enzyme System
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Mixed Function Oxygenases
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CYP3A protein, human
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Cytochrome P-450 CYP3A
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CYP3A4 protein, human
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NADPH-Ferrihemoprotein Reductase
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Glutathione
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Magnesium
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Calcium