Atrazine, glutathione conjugation

We have synthesized the glutathione conjugate of tridiphane and shown it to be inactive as a herbicide however, G. L. Lamoureux and D. G. Rusness (14,15) have found it to be an effective inhibitor of atrazine glutathione conjugation in vitro. 

Figure 7.2 Metabolism of atrazine in sugarcane plants by (a) ALdcal kylation of the side chains, (b) hydrolysis of the 2-chloro group followed by JV-dealkylation, and (c) displacement of the 2-chloro by glutathione conjugation (Larson and Ash, 1993).

Lamoureux, G.L., L.E. Stafford, R.H Shimabukuro, and R.G. Zaylskie (1973). Atrazine metabolism in sorghum Catabolism of the glutathione conjugate of atrazine. J. Agric. Food Chem., 21 1020-1030. 

Shimabukuro, R.H., D.S. Frear, S.H.R. Swanson, and W.C. Walsh (1971b). Glutathione conjugation An enzymatic basis for atrazine resistance in corn. Plant Physiol., 47 10-14. 

Gray, J.A., N.E. Balke, and D.E. Stoltenberg (1996). Increased glutathione conjugation of atrazine confers resistance in a Wisconsin vel-vetleaf (Abutilon theophrasti) biotype. Pestic. Biochem. Physiol., 55 157-171. 

The basis of the selectivity and differences in type of activity of the triazines has been discussed thoroughly conjugation with glutathione, via displacement of the chlorine. 

The third metabolic pathway discovered for degradation of triazine herbicides in plants was first reported by Shimabukuro et al. (1970) and involved conjugation of atrazine with glutathione in corn nutrient uptake, excised leaves, and leaf disc experiments. This new degradation mechanism was postulated to be the primary factor in the... 

Although no specific metabolites have been identified, atrazine has been shown to turnover cytosolic glutathione 5-transferase indicating conjugation in zebrafish, rainbow trout, starry flounder (.Platichthys stellatus) and English sole (.Pleuronectes vetulus)22,90. Approximately 50% of atrazine was converted to four uncharacterized metabolites in zebrafish36. 

The conjugation of xenobiotics with glutathione (GSH) in higher plants was first demtxistrated to be a major enzymatic detoxication mechanism with the atrazine herbicide in sorghum, corn, and other atrazine resistant species (77-80) (Equation 15). Since this... 

Glutathione S-transferase enzymes have been detected In a variety of different plant species (24,76.64.97.101.107-110). Howevei, detailed enzyme studies have been limited to corn (24.76, J09., 12 ) and pea (. JOT., 110). The foliar tissue of corn contains a GST Isozyme that appears rather unique In Its ability to catalyze the conjugation of various 2-chloro-s-trlazlnes with GSH (78). The molecular weight and other properties of this Isozyme are similar to those reported for many mammalian GST Isozymes however, the pH optimum of this Isozyme for atrazine Is somewhat lower than that reported for many GST Isozymes (, 78,J09.). When corn Is treated with R-25788, a second Isozyme Is Induced ( ). The Induced Isozyme Is very effective In catalyzing the GSH conjugation of an a-chloroacetamlde herbicide (alachlor), but It was not assayed with atrazine ( ). 

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