Anthranilate synthase feedback inhibition

Enzymes catalyzing the conversions from chorismate (37), namely, CM and anthranilate synthase (AS) (Figure 6), are also subject to feedback regulation. CM is inhibited by Phe (1) and Tyr (2), and activated by... 

In B. subtilis, the pathway from chorismate to tryptophan is feedback-inhibited by tryptophan, which suppresses anthranilate synthase activity. Mutant B. subtilis that lacks tryptophan synthetase can grow on minimal medium only when supplemented with exogenous tryptophan. Under these conditions, none of the intermediates in the tryptophan biosynthetic pathway from anthranilate to indole 3-glycerol phosphate are produced. However, when the bacteria have depleted the medium of tryptophan, the levels of those intermediates increase, even though there is no net production of tryptophan. Why ... 

Studies with isolated enzymes in vitro reveal feedback inhibition of chorismate mutase by phenylalanine and tyrosine. Tryptophan apparently controls its own synthesis by feedback inhibition of anthranilate synthase and furthermore exerts control in the partitioning of chorismate between the two competing routes of chorismate metabolism by its ability to both activate chorismate mutase and relieve the inhibition imposed on this step by phenylalanine and tyrosine. In addition, carbon flux throuch chorismate to prephenate is also sensitive to fluctuations in chorismate concentration due to the allosteric substrate activation of chorismate mutase by chorismate. 

Fig. 9. Sequential pattern of allosteric control over biosynthesis of aromatic amino acids in the plastid compartment. In the presence of excess aromatic amino acids, L-tyrosine (TYR) inhibits arogenate dehydrogenase, L-phenylalanine (PHE) inhibits arogenate dehydratase and L-tryptophan (TRP) inhibits anthranilate synthase. The three aromatic amino acids exert allosteric inhibition (-) or activation (+) effects upon chorismate mutase-1 as symbolized. However, activation dominates over inhibition. The outcome of these events is to trap L-arogenate (AGN) between the various foci of control in the pathway. As shown symbolically, -arogenate (AGN) then acts to feedback inhibit DAHP synthase-Mn.

Tryptophan pool size is regulated by feedback inhibition of anthranilate synthase by tryptophan. Other mechanisms, as yet unidentified, may regulate tryptophan and indoleacetic acid synthesis. 

The availability of tryptophan is also a determining factor in the formation of indoleacetic acid the pool size of tryptophan is regulated in part by tryptophan feedback inhibition of anthranilate synthase. 

Chorismate serves as the branch point metabolite for the synthesis of tryptophan or phenylalanine and tyrosine. The branch of the pathway leading to tryptophan is considered to be tightly regulated by feedback inhibition of the first committed reaction, catalyzed by anthranilate synthase (8). This is supported by the observation that cells containing tryptophan-resistant anthrani-... 

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