Tryptophan enzyme synthesis regulation

Ito and Crawford [132] studied repression control by tryptophan of the enzyme products of the five tryptophan genes in E. coli. They found that synthesis of all the enzymes assayed (AS, PRT, InGPS, TS-B, and TS-A) was repressed in the presence of tryptophan and that removal of tryptophan resulted in coordinate derepression. In addition they confirmed the finding of Cohen and Jacob [15] that constitutive tryptophan enzyme synthesis resulted from mutation of a regulator locus (currently called trpR) unlinked to the tryptophan genes, but linked to a threonine (thr) locus. Bauerle and Margolin [133], studying the tryptophan enzymes in S. typhimurium, found what they referred to as semicoordinate... 

C29 Cihak, A., Wilkinson, D. and Pitot, H. C. The effect of pyrimidine analogues and tryptophan on enzyme synthesis and degradation in rat liver. Adv. Enzyme Regul., 9, 267-289 (1970)... 

As described in a previous section, five structural genes have been identified in the tryptophan operons of E. coli and S. typhimurium (Fig. 3). At one end of the cluster is the promoter, PI, and the operator, which serve, respectively, as the site for initiation of transcription and as a target for the repressor and together largely determine the level of expression of the structural genes. As mentioned in the section on regulation of enzyme synthesis, there is evidence for an internal promoter-like... 

PAH, a nonheme iron-containing enzyme, is a member of a larger BI Independent amino acid hydroxylase family. In addition to PAH, the enzyme family includes tyrosine hydroxylase and tryptophan hydroxylase. The enzymes in this family participate in critical metabolic steps and are tissue specific. PAH catabolizes excess dietary PA and synthesizes tyrosine. In adrenal and nervous tissue, tyrosine hydroxylase catalyzes the initial steps in the synthesis of dihydrox-yphenylalanine. In the brain, tryptophan is converted to 5-hydroxytryptophan as the first step of serotonin synthesis. Consequently, these enzymes are highly regulated not only by their expression in different tissues but also by reversible phosphorylation of a critical serine residue found in regulatory domains of the three enzymes. Since all three enzymes are phosphorylated and dephosphorylated by different kinases and phosphatases in response to the need for the different synthetic products, it is not unexpected that the exact regulatory signal for each member of the enzyme family is unique. 

Fig. 6. Regulation of the synthesis of aromatic amino acids in plants. Each of the sequential arrows represents the enzyme catalyzed steps detected in Figs. 2, 3 and 4. Bold lines indicate inhibition of chorismate mutase by phenylalanine and tyrosine in addition to anthranilate synthase inhibition by tryptophan. The dashed arrow symbolizes the ability of tryptophan to both activate chorismate mutase and antagonize inhibition of this enzyme by either phenylalanine or tyrosine.

Because both tryptophan and tyrosine participate in melanogenic processes, the possible influence of different enzymes like tyrosinase, tryptophan pyrrolase (TP), indoleamine 2,3-dioxygenase (lOD), and tyrosine aminotransferase (TAT) on the regulation of melanin synthesis as it relates to vitiligo has been depicted in Fig. 8, which constitutes a modification of the Raper-Mason scheme for melanin synthesis (53, 54). 

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]. 

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