Inhibition of Aromatic Amino Acid Production
Now that you understand the importance of EPSP Synthase, we will look at how glyphosate functions as a herbicide. The chemical structures of PEP and glyphosate are very similar as seen in Figure 11.
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 (Fig 12).
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) (Fig 13). 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.
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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.