Linked Life Data

15479032

Source:http://linkedlifedata.com/resource/pubmed/id/15479032

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2004-10-13
pubmed:abstractText
Biochanin A and formononetin are the predominant isoflavones in red clover. In a previous study (J. Agric. Food Chem. 2002, 50, 4783-4790), it was demonstrated that human liver microsomes converted biochanin A and formononetin to genistein and daidzein. This paper now shows CYP1B1-catalyzed O-demethylation of biochanin A and formononetin to produce genistein and daidzein, respectively, which inhibit CYP1B1. Recombinant human CYP1A1 or CYP1B1 was incubated with biochanin A or formononetin. CYP1A1 catalyzed isoflavone 4'-O-demethylation and hydroxylations with similar efficiency, whereas CYP1B1 favored 4'-O-demethylation over hydroxylations. Three of the biochanin A metabolites (5,7,3'-trihydroxy-4'-methoxyisoflavone, 5,7,8-trihydroxy-4'-methoxyisoflavone, and 5,6,7-trihydroxy-4'-methoxyisoflavone) were characterized by 1H NMR spectroscopy and mass spectrometry. Daidzein (Ki = 3.7 microM) exhibited competitive inhibition of CYP1B1 7-ethoxyresorufin O-deethylase activity, and genistein (Ki = 1.9 microM) exhibited mixed inhibition. Biochanin A and/or formononetin may exert anticarcinogenic effects directly by acting as competitive substrates for CYP1B1 or indirectly through their metabolites daidzein and genistein, which inhibit CYP1B1.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-8561
pubmed:author
pubmed:copyrightInfo
Copyright 2004 American Chemical Society
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
52
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6623-32
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Inhibition of extrahepatic human cytochromes P450 1A1 and 1B1 by metabolism of isoflavones found in Trifolium pratense (red clover).
pubmed:affiliation
Division of Biochemical Toxicology, National Center for Toxicological Research, 3900 NCTR Road, Jefferson, Arkansas 72079, USA.
pubmed:publicationType
Journal Article