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Experimental methods to elucidate the toxic effects of organophosphates on GSTM and GSTP
Başlık:
Experimental methods to elucidate the toxic effects of organophosphates on GSTM and GSTP
Yazar:
Alghamdi, Ali A., author.
ISBN:
9780438078925
Yazar Ek Girişi:
Fiziksel Tanımlama:
1 electronic resource (74 pages)
Genel Not:
Source: Masters Abstracts International, Volume: 57-06M(E).
Advisors: Kathleen M. Frey.
Özet:
Organophosphates (OPs) are one of the most widely used and most effective insecticides around the world. OPs can have adverse health effects from exposure due to contaminated food or water sources. Glutathione S-transferase enzymes (GSTs) are a group of phase II enzymes that work by catalyzing the conjugation of glutathione (GSH) on electrophilic xenobiotics. GSTM and GSTP isoforms are expressed in all body cells. GSTM is present mainly in the liver, while GSTP is present mainly in the brain and lungs. The objective of this study is to experimentally study the toxic effect of different OPs binding to GSTM and GSTP. In this study, we used spectrophotometric assays to test the inhibition of Dibrom (DB), Dialifos (DF), and Chlorpyrifos (CP). Our results show that OPs can inhibit the activity of GST enzymes. The results were supported by a crystal structure of GSTP. GSTP was co-crystallized with GSH and CP and the resulting crystals diffracted to 1.5 A. The crystal structure revealed that CP binds an allosteric binding site near the N-terminal domain. Kinetic assay results extrapolated to Lineweaver-Burke reveal a noncompetitive inhibition binding mode. To our knowledge, this is the first study to demonstrate noncompetitive inhibition of OPs on GSTs. Most significantly, this study suggests a molecular mechanism of toxicity for OP pesticides.
Notlar:
School code: 0198
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