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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
3
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pubmed:dateCreated |
1991-6-5
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pubmed:abstractText |
A human cytochrome P4502C9 cDNA clone has been isolated from a human liver bacteriophage Lambda gt11 library using oligonucleotide probes. Expression of the 1762 base pair cDNA in COS cells demonstrated that the encoded enzyme has a molecular mass of 55 kDa as determined by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The expressed enzyme catalysed the methylhydroxylation of tolbutamide with an apparent Km of 131.7 microM, similar to that observed in human liver microsomes. P4502C9 also catalysed the 4-hydroylation of phenytoin, and inhibition experiments demonstrated that phenytoin was a competitive inhibitor of tolbutamide hydroxylation with an apparent Ki of 19.1 microM. Sulphaphenazole was a potent inhibitor of the expressed enzyme with respect to both tolbutamide and phenytoin hydroxylations. These data demonstrate that a single isozyme can catalyse the hydroxylations of both tolbutamide and phenytoin, and suggest that both reactions are mediated by the same isozyme(s) of cytochrome P450 in human liver.
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pubmed:commentsCorrections |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0006-291X
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
29
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pubmed:volume |
175
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1112-8
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:2025243-Animals,
pubmed-meshheading:2025243-Base Sequence,
pubmed-meshheading:2025243-Cell Line,
pubmed-meshheading:2025243-Cytochrome P-450 Enzyme System,
pubmed-meshheading:2025243-DNA,
pubmed-meshheading:2025243-Gene Library,
pubmed-meshheading:2025243-Humans,
pubmed-meshheading:2025243-Hydroxylation,
pubmed-meshheading:2025243-Kinetics,
pubmed-meshheading:2025243-Liver,
pubmed-meshheading:2025243-Microsomes, Liver,
pubmed-meshheading:2025243-Molecular Sequence Data,
pubmed-meshheading:2025243-Oligonucleotide Probes,
pubmed-meshheading:2025243-Phenytoin,
pubmed-meshheading:2025243-Recombinant Proteins,
pubmed-meshheading:2025243-Substrate Specificity,
pubmed-meshheading:2025243-Sulfaphenazole,
pubmed-meshheading:2025243-Tolbutamide,
pubmed-meshheading:2025243-Transfection
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pubmed:year |
1991
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pubmed:articleTitle |
Tolbutamide and phenytoin hydroxylations by cDNA-expressed human liver cytochrome P4502C9.
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pubmed:affiliation |
Department of Clinical Pharmacology, School of Medicine, Flinders University of South Australia, Adelaide.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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