Interaction of chlorophenoxyalkyl acid herbicides with rat-liver glutathione S-transferases.
The in vitro interaction of four chlorophenoxyalkyl (CPA) acid herbicides with rat-liver glutathione S-transferase (GST) was studied using reduced glutathione and 1-chloro-2,4-dinitrobenzene as substrates. Inhibition of GST activity by the CPA acids in crude extracts was dose dependent. Ring substitution and side-chain length were shown to be of importance in determining the extent of GST inhibition. While GST AA, an isoenzyme of GST, was stimulated by two CPA acids, each of the other GST isoenzymes (A, B, C, E and M) was inhibited, to different degrees. Kinetic studies revealed a mixed type inhibition of the isoenzymes. Conjugates of CPA acids with glutathione were not formed. These results indicate that CPA acids interact with GST by binding directly to these proteins, possibly at a different locus from that of the substrate. The binding of CPA acids to GST may, therefore, have a protective function against these herbicides.
D015084:2,4-Dichlorophenoxyacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008456:2-Methyl-4-chlorophenoxyacetic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006540:Herbicides / Q000378:metabolism / Q000494:pharmacology*; D066298:In Vitro Techniques; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D011485:Protein Binding; D051381:Rats; D011919:Rats, Inbred Strains
D006540:Herbicides; D007527:Isoenzymes; D015084:2,4-Dichlorophenoxyacetic Acid; C008340:mecoprop; D008456:2-Methyl-4-chlorophenoxyacetic Acid; D005982:Glutathione Transferase; C010571:dichlorprop