Chorismic acid, tryptophan synthesis feedback inhibition

The synthesis of tryptophan in microorganisms is affected at several levels by end-product inhibition. Thus, end-product feedback inhibition partly regulates the synthesis of chorismic acid which is the final product of the common aromatic pathway and serves as a substrate for the first reaction in the tryptophan-synthesizing branch pathway (see Fig. 2). Regulation of the common aromatic pathway was recently reviewed by Doy [72]. The first enzyme of the common aromatic pathway, 3-deoxy-D-flrah/>jo-heptulosonate 7-phosphate synthetase (DAHPS), has been reported to exist as at least three isoenzymes, each specifically susceptible to inhibition by one of the aromatic amino acid end products (tyrosine, phenylalanine, and tryptophan), in E. coli (see reference [3]). It should be noted that many reports have indicated that in E. coli the DAHPS (trp), the isoenzyme whose synthesis is repressed specifically by tryptophan, was not sensitive to end-product inhibition by tryptophan. Recently, however, tryptophan inhibition of DAHPS (trp) activity has been demonstrated in E. coli [3,73,74]. The E. coli pattern, therefore, represents an example of enzyme multiplicity inhibition based on the inhibition specificity of isoenzymes. It is interesting to note the report by Wallace and Pittard [75] that even in the presence of an excess of all three aromatic amino acids enough chorismate is synthesized to provide for the synthesis of the aromatic vitamins whose individual pathways branch from this last common aromatic intermediate. In S. typhimurium, thus far, only two DAHPS isoenzymes, DAHPS (tyr) and DAHPS (phe) have been identified as sensitive to tyrosine and phenylalanine, respectively [76]. 

The feedback inhibition control described above provides one form of regulation of the synthesis of chorismic acid which serves as a substrate in the first reaction specific to the tryptophan branch pathway. In the same reaction glutamine serves as the amino donor [80,81] in the... 

End-product inhibition of AS activity by tryptophan appears to be a rather common control mechanism among microorganisms. Nester and Jensen [71] described tryptophan inhibition of B. subtilis AS activity as the first step in sequential feedback control. Excess tryptophan would result in inhibition of the conversion of chorismate to anthrani-late. The consequent accumulation of chorismic acid would then serve as a feedback inhibitor of the DAMPS, the first enzyme in the pathway leading to chorismate synthesis. Bacillus alvei has an anthranilate synthetase which is extremely sensitive to inhibition by tryptophan [98]. In contrast to the mode of AS feedback inhibition in E. coli and S. typhimurium, the B. alvei AS is inhibited by tryptophan noncom-petitively with respect to chorismate and uncompetitively with respect to glutamine. It is the only Bacillus species, among 21 studied, which did not exhibit a sequential feedback control pattern [79]. 

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