Linked Life Data

14976351

Source:http://linkedlifedata.com/resource/pubmed/id/14976351

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-4-9
pubmed:abstractText
The flavin-containing monooxygenase gene family (FMO1-6) in humans encodes five functional isoforms that catalyze the monooxygenation of numerous N-, P- and S-containing drugs and toxicants. A previous single nucleotide polymorphism (SNP) analysis of FMO1 in African-Americans identified seven novel SNPs. To determine the functional relevance of the coding FMO1 variants (H97Q, I303V, I303T, R502X), they were heterologously expressed using a baculovirus system. Catalytic efficiency and stereoselectivity of N- and S-oxygenation was determined in the FMO1 variants using several substrates. The I303V variant showed catalytic constants equal to wild-type FMO1 for methimazole and methyl p-tolyl sulfide. Catalytic efficiency (V(max)/K(m)) of methyl p-tolyl sulfide oxidation by R502X was unaltered. In contrast, methimazole oxidation by R502X was not detected. Both H97Q and I303T had elevated catalytic efficiency with regards to methyl p-tolyl sulfide (162% and 212%, respectively), but slightly reduced efficiency with regards to methimazole (81% and 78%). All the variants demonstrated the same stereoselectivity for methyl p-tolyl sulfide oxidation as wild-type FMO1. FMO1 also metabolized the commonly used insecticide fenthion to its (+)-sulfoxide, with relatively high catalytic efficiency. FMO3 metabolized fenthion to its sulfoxide at a lower catalytic efficiency than FMO1 (27%) and with less stereoselectivity (74% (+)-sulfoxide). Racemic fenthion sulfoxide was a weaker inhibitor of acetylcholinesterase than its parent compound (IC(50) 0.26 and 0.015 mM, respectively). The (+)- and (-)-sulfoxides were equally potent inhibitors of acetylcholinesterase. These data indicate that all the currently known FMO1 variants are catalytically active, but alterations in kinetic parameters were observed.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1096-6080
pubmed:author
pubmed:issnType
Print
pubmed:volume
78
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
196-203
pubmed:dateRevised
2010-9-17
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Evaluation of xenobiotic N- and S-oxidation by variant flavin-containing monooxygenase 1 (FMO1) enzymes.
pubmed:affiliation
Environmental Toxicology Program, University of California, Riverside, California 92521, USA. bfurnes@citrus.ucr.edu
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't