Linked Life Data

1492424

Source:http://linkedlifedata.com/resource/pubmed/id/1492424

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1993-3-2
pubmed:abstractText
1. Pyrrolizidine alkaloids (PAs) are metabolized primarily to putative dehydroalkaloid (PA pyrrole) metabolites and to PA N-oxide by rat liver microsomal monooxygenases. 2. The dehydroalkaloids are highly reactive and either bind covalentely to tissue nucleophiles or are hydrolysed to the more stable pyrrole, (R,S)-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine (DHP), and the corresponding necic acid. 3. Addition of glutathione (GSH 1 mM) to incubation mixtures containing rat liver microsomes and the PA senecionine (SN), resulted in the formation of a conjugate of DHP with GSH. 5. The mass spectrum of this DHP-GSH conjugate was identical to that of the chemically-synthesized dehydroretronecine (the R enantiomer of the racemic DHP) and GSH. 6. Only negligible amounts of DHP-GSH conjugate were formed when DHP itself was incubated with GSH at physiological pH. 7. These findings provide strong evidence for the microsomal conversion of SN to a highly reactive metabolite, presumably dehydrosenecionine, which then reacts with GSH to form the DHP-GSH conjugate. 8. It is likely that a similar mechanism is responsible in vivo for the formation of GSH conjugates of DHP from SN and other PAs.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0049-8254
pubmed:author
pubmed:issnType
Print
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1321-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1992
pubmed:articleTitle
Microsomal formation of a pyrrolic alcohol glutathione conjugate of the pyrrolizidine alkaloid senecionine.
pubmed:affiliation
Department of Agricultural Chemistry, Oregon State University, Corvallis.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S.