Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
19
pubmed:dateCreated
2008-8-7
pubmed:abstractText
Previous lab studies implicated the sulfoxidation pathway of molinate metabolism to induce testicular toxicity. Once molinate is metabolized to molinate sulfoxide, it undergoes further phase II metabolism either spontaneously, enzyme catalyzed, or both to form glutathione-conjugated molinate. This study compared the metabolic capability of rat and human liver cytosol to form a glutathione (GSH)-conjugated metabolite of molinate. The GSH conjugation of molinate sulfoxide in rat cytosol was described by the constants Km of 305 microM and Vmax of 4.21 nmol/min/mg cytosol whereas the human values were 91 microM and 0.32 nmol/min/mg protein for Km and Vmax, respectively. At the same 1 mM GSH concentration, the in vitro bimolecular nonenzymatic rate constant of 3.02 x 10(-6) microM(-1) min(-1) was calculated for GSH conjugation of molinate sulfoxide. Specific activity for rat and human glutathione transferase was calculated to equal 1.202 +/- 0.25 and 0.809 +/- 0.45 micromol/min/mg protein, respectively by 1-chloro-2,4-dinitrobenzene (CDNB) assay. Compared to a conventional GSH depletion model (BSO + DEM combination), molinate alone was nearly as effective in reducing GSH levels by approximately 90 and 25% in liver and testes, respectively. The impact of molinate sulfoxide's ability to adduct glutathione transferase and inhibit the production of the glutathione conjugated metabolite was examined and found to be negligible.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
1528-7394
pubmed:author
pubmed:issnType
Print
pubmed:volume
71
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1338-47
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Detoxification of molinate sulfoxide: comparison of spontaneous and enzmatic glutathione conjugation using human and rat liver cytosol.
pubmed:affiliation
Department of Environmental Toxicology, UC Davis, Davis, California, USA. arc40@astound.net
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural