Linked Life Data

11599930

Source:http://linkedlifedata.com/resource/pubmed/id/11599930

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2001-10-15
pubmed:abstractText
The rat esophagus is strikingly sensitive to tumor induction by nitrosamines, and it has been hypothesized that this tissue contains cytochrome P450 enzymes (P450s) which catalyze the metabolic activation of these carcinogens. The metabolic capacity of the esophagus is not well characterized. In the study described here, the products of 14C-coumarin metabolism by rat esophageal microsomes were identified and quantified. Metabolite characterization was by LC/MS/MS and GC/MS and comparison to standards, quantification was by radioflow HPLC. The coumarin metabolites formed by rat esophageal microsomes were compared to those formed by P450 2A3. The major metabolites formed by esophageal microsomes were 8-hydroxycoumarin, o-hydroxyphenylacetaldehyde (o-HPA), and o-hydroxyphenylacetic acid (o-HPAA). A smaller amount of 5-hydroxycoumarin, about one-third the 8-hydroxycoumarin, was also formed. o-HPA and o-HPAA are products of coumarin 3,4-epoxidation. The relative rates of coumarin 8-hydroxylation and 3,4-epoxidation were similar. Coumarin 8-hydroxylation has not previously been reported as a major pathway in any tissue, and no P450s have yet been reported to catalyze this reaction. P450 2A3 catalyzed both the 7-hydroxylation and 3,4-epoxidation of coumarin. P450 2A3 was previously characterized as a coumarin 7-hydroxylase, however, in this study, we report that it catalyzes the formation of o-HPA more efficiently. The Km and Vmax were 1.3 +/- 0.35 microM and 0.65 +/- 0.06 nmol/min/nmol P450 for coumarin 7-hydroxylation and 1.4 +/- 0.58 microM and 3.1 +/- 0.46 nmol/min/nmol P450 for o-HPA formation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0893-228X
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1386-92
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Coumarin metabolism by rat esophageal microsomes and cytochrome P450 2A3.
pubmed:affiliation
Department of Biochemistry, Molecular Biology & Biophysics, University of Minnesota Cancer Center, Minneapolis, Minnesota 55455, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.