Source:http://linkedlifedata.com/resource/pubmed/id/15258113
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
8
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pubmed:dateCreated |
2004-7-19
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pubmed:abstractText |
Metabolism of polychlorinated dibenzo-p-dioxins by cytochrome P450 (P450) and UDP-glucuronosyltransferase (UGT) was examined using a recombinant enzyme system and human liver microsomes. We analyzed the glucuronidation of 2,3,7-trichlorodibenzo-p-dioxin (2,3,7-triCDD) by rat CYP1A1 expressed in yeast microsomes and human UGT expressed in baculovirus-infected insect cells. Multiple UGT isozymes showed glucuronidation activity toward 8-hydroxy-2,3,7-triCDD (8-OH-2,3,7-triCDD), which was produced by CYP1A1. Of these UGTs, UGT1A1, 1A9, and 2B7, which are constitutively expressed in human livers, showed remarkable activity toward 8-OH-2,3,7-triCDD. The apparent kinetic parameters of glucuronidation, K(m) and k(cat), were estimated to be 0.8 microM and 1.8 min(-1), respectively, for UGT1A1, 0.8 microM and 1.8 min(-1), respectively, for UGT1A9, and 3.9 microM and 7.0 min(-1), respectively, for UGT2B7. In human liver microsomes with NADPH and UDP-glucuronic acid, 2,3,7-triCDD was first converted to 8-OH-2,3,7-triCDD, then further converted to its glucuronide. We compared the ability of 10 human liver microsomes to metabolize 2,3,7-triCDD and observed a significant difference in the glucuronidation of 2,3,7-triCDD that originated from the difference of the P450-dependent hydroxylation of 2,3,7-triCDD.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0090-9556
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
32
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
870-5
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:15258113-Animals,
pubmed-meshheading:15258113-Cytochrome P-450 Enzyme System,
pubmed-meshheading:15258113-Dose-Response Relationship, Drug,
pubmed-meshheading:15258113-Glucuronosyltransferase,
pubmed-meshheading:15258113-Humans,
pubmed-meshheading:15258113-Microsomes, Liver,
pubmed-meshheading:15258113-Rats,
pubmed-meshheading:15258113-Tetrachlorodibenzodioxin
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pubmed:year |
2004
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pubmed:articleTitle |
Sequential metabolism of 2,3,7-trichlorodibenzo-p-dioxin (2,3,7-triCDD) by cytochrome P450 and UDP-glucuronosyltransferase in human liver microsomes.
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pubmed:affiliation |
Graduate School of Agrculture, Kyoto University, Kyoto, Japan.
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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