Trialkyl phosphorothioates and glutathione S-transferases

Area of Science:

• Biochemistry
• Enzymology
• Toxicology

Background:

• Glutathione S-transferases (GSTs) are crucial enzymes involved in detoxification.
• Trialkyl phosphorothioates are a class of organophosphorus compounds with potential toxicological relevance.

Purpose of the Study:

• To investigate the interaction of specific trialkyl phosphorothioates with rat liver glutathione S-transferases.
• To determine the substrate specificity and catalytic efficiency of GSTs towards these compounds.

Main Methods:

• Enzyme assays using rat liver cytosol.
• Fractionation of liver cytosol to identify active GST isozymes.
• Characterization of methyl transfer from phosphorothioates to glutathione.

Main Results:

• Trialkyl phosphorothioates were confirmed as substrates for rat liver GSTs.
• OSS-trimethyl phosphorodithioate (OSS-Me(O)) was identified as a general substrate for GSTs.
• The methyl group transferred to glutathione originated from the oxygen-linked phosphorus atom.
• Specific activity with OSS-Me(O) was significantly lower compared to standard GST substrates like dinitrobenzene derivatives.

Conclusions:

• Rat liver GSTs can metabolize certain trialkyl phosphorothioates.
• While several GST isozymes contribute to the overall activity, OSS-Me(O) exhibits broad substrate acceptance.
• The low specific activity suggests a limited role for these specific phosphorothioates in major GST-mediated detoxification pathways.