Linked Life Data

19059219

Source:http://linkedlifedata.com/resource/pubmed/id/19059219

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2009-2-16
pubmed:abstractText
The capacity to oxidize bufuralol (BF) and dextromethorphan (DEX) was compared kinetically between human CYP2D6 and four rat CYP2D (CYP2D1, -2D2, -2D3 and -2D4) isoenzymes in a yeast cell expression system. In BF 1''-hydroxylation and DEX O-demethylation, only CYP2D4 showed hook-shaped Eadie-Hofstee plots, the other four CYP2D enzymes exhibiting linear plots. In DEX N-demethylation, rat CYP2D2 did not show any detectable activity under the conditions used, whereas the other four enzymes yielded linear Eadie-Hofstee plots. To elucidate the mechanisms causing the nonlinear kinetics, four CYP2D4 mutants, CYP2D4-F109I, -V123F, -L216F and -A486F, were prepared. CYP2D4-V123F, -L216F and -A486F yielded linear or linear-like Eadie-Hofstee plots for BF 1''-hydroxylation, whereas only CYP2D4-A486F exhibited linear plots for DEX O-demethylation. The substitution of Phe-109 by isoleucine did not have any effect on the oxidative capacity of CYP2D4 for either BF or DEX. These results suggest that the introduction of phenylalanine in the active-site cavity of CYP2D4 simplifies complicated interactions between the substrates and the amino acid residues, but the mechanisms causing the simplification differ between BF and DEX.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1873-2968
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
77
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
920-31
pubmed:dateRevised
2009-5-21
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
The mechanism causing the difference in kinetic properties between rat CYP2D4 and human CYP2D6 in the oxidation of dextromethorphan and bufuralol.
pubmed:affiliation
Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka, Okayama 700-8530, Japan. shizuo@pharm.okayama-u.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't