Chapter 16: MOA Part 2: Amino Acid Synthesis Inhibitors & Nitrogen Metabolism Inhibitors

16.7 Herbicides that Inhibit EPSP Synthase

The following animation visually depicts the main part of the shikimate pathway we are most interested in.  It also shows how the herbicide, glyphosate, interferes with the pathway.  You can either click through the animation on your own and/or watch the video clip of Dr. Namuth-Covert explaining the animation.

Please note the animation requires Flash player.  If you are utilizing a mobile device, we recommend viewing the video.

Access the EPSP Synthase Animation Here: http://passel.unl.edu/pages/animation.php?a=EnzymeAction.swf

Interesting Glyphosate Facts

Glyphosate, one of the most successful herbicides ever discovered, inhibits the production of aromatic amino acids: phenylalanine, tyrosine, and tryptophan. Glyphosate is a potent inhibitor of 5-enolpyruvylshikimate-3-phosphate synthase (often referred to as EPSP synthase or EPSPS).

The chemical structures of PEP (from the shikimate pathway) and glyphosate are very similar.  As a result, glyphosate acts as a competitive inhibitor of PEP and binds more tightly to the EPSP synthase-S3P complex than does the normal substrate PEP. However, like PEP, glyphosate has no affinity for the enzyme alone. A major difference between glyphosate and PEP is that the dissociation rate for glyphosate is 2,300 times slower than PEP. Therefore, once glyphosate binds the enzyme-substrate complex (EPSP synthase-S3P) the enzyme is essentially inactivated.

Glyphosate can also be considered an uncompetitive inhibitor of EPSP synthase with respect to S-3-P. There are other factors that contribute to glyphosate’s herbicidal activity. The shikimate pathway is normally controlled by a process called feedback inhibition. In the shikimate pathway, arogenate (a product of the pathway) is a potent inhibitor of the first enzyme in the shikimate pathway, 3-deoxy-D-arabino-heptulosonate-7-phosphate synthase (DAHP synthase). Inhibition of EPSP synthase by glyphosate results in the decreased levels of arogenate causing the deregulation of the shikimate pathway due to increased DAHP synthase activity.

Deregulating the shikimate pathway results in the accumulation of very high levels of shikimate and S3P and in some plant species this accumulation can account for up to 16% of plant dry weight in sink tissues. Important building blocks for other metabolic pathways are reduced by uncontrolled carbon flow through the shikimate pathway and reduced levels of aromatic amino acids causes significant reductions in protein synthesis.

Organophosphorus (Group 9)

** Glyphosate Technical Fact Sheet. National Pesticide Information Center. http://npic.orst.edu/factsheets/archive/glyphotech.html

Review and Reflection

 

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Principles of Weed Control Copyright © by Deana Namuth-Covert and Amy Kohmetscher. All Rights Reserved.