Histidine synthesis

Regulation of histidine synthesis. In all, ten different genes code for the enzymes of histidine biosynthesis in Salmonella typhimurium. They are clustered as the histidine operon, a consecutive series of genes which are transcribed into messenger RNA as a unit.250 251 The gene symbols His A, HisB, etc., are indicated in Fig. 25-13, and their positions on the E. coli gene map are indicated in Fig. 26-4. The gene HisB codes for a complex protein with two different enzymatic activities as shown in Fig. 25-13. 

Figure 2-2 Bioluminescent Salmonella assay workflow. The luminescent histidine-dependent cells are exposed to tested compounds in agar overlay containing only traces of histidine in multiwell-plate format. The reverse-mutation events restore endogenous histidine synthesis resulting in luminescent colonies of histidine-independent cells that can be visualized via CCD camera. The fully automated instrument in conjunction with automated image analysis of plates enables the analysis of 100 plates in one run.

Studies of the mechanisms of histidine synthesis in lactic acid bac-... 

Winter et al. (1971a) also attempted to obtain evidence for the derepression of IGP dehydratase by growing plants in the presence of aminotriazole, which inhibits histidine synthesis and thus should cause derepression as it does in bacteria. However the results obtained did not suggest that derepression was occurring in higher plants. 

In several syntheses, nitrogen is derived directly from the amide group of L-glutamine, e.g. in histidine synthesis conversion of chorismate into anthranilate (see Tryptophan synthesis) synthesis of amino sugars amination of UTP to CTP. 

The pathway of histidine biosynthesis, as it is now known, is shown in Fig. 3-1. The N-1 and C-2 of ATP, and the ribose-P w hich becomes bound to its N-1 position, provide the skeleton of histidine, while the phospho-ribosyl aminoimidazole carboxamide remnant is released. As is shown in Chapter 7, phosphoribosjd aminoimidazole carboxamide is an intermediate in the pathway of purine biosynthesis de novo, and so histidine synthesis not only provides a branch leading into this pathway, but actually makes a loop. 

In some microorganisms the conversion of adenylate to inosinate takes place via the reactions of histidine synthesis from ATP, as described in Chapter 3. 

If on the basis of the studies of mutants, one places all the segments of the operon in sequence as they appear in the chromosome, the sequence of Table 2-7 is obtained. Although the genes controlling histidine synthesis are arranged in a cluster, they are clearly not inserted in the operon in a sequence that corresponds to the sequence of steps in the metabolic pathway. 

Glutamate, on the other hand, does not appear to be a direct precursor in histidine synthesis. In experiments with yeast grown on a medium containing inert L-glutamate and radioactive uniformly labeled glucose, the histidine was found to be highly radioactive. This appears to demon-... 

The D-erythro configuration of imidazoleglycerol suggests that a pentose such as ribose 5 -phosphate might be concerned in the formation of the above intermediates of histidine synthesis. Qualitative evidence has been obtained of an enzyme that converts imidazoleglycerol phosphate to imidazoleacetol phosphate ( SS, 84). The further characterization of this enzyme has not been reported. 

Negative repression was investigated in the tryptophan (trp) synthesis operons of E. coli and Salmonella typhimurium, and the histidine synthesis operon of Salmonella. The trp operon is totally derepressed in the presence of nonsurplus amounts of tryptophan. Here, transcription and translation go at maximal rates. Enzymes of the tryptophan system synthesized it in amounts which are totally utilized during translation. This condition is known as turn on. The activity of the first enzyme in the sequence of tryptophan synthesis — anthranilate synthetase — is inhibited within several seconds after the addition of surplus tryptophan. The aporepressor becomes the repressor and inhibits transcription of the operon (negative repression) after it associates with the effector, tryptophan. This association occurs if the surplus of tryptophan exists for a sufficient amount of time. After several minutes, most of the resulting mRNA is degraded and the rate of synthesis is noticeably reduced (known as the turn of condition). 

The temporal genome organization of eukaryotes could have evolved from the functional organization of the prokaryotic genome. The temporal sequence of protein synthesis in prokaryotes occurs from a stable, polycistronic template which is determined by the linear sequence of cistrons (Ohtaka and Spiegelman, 1963). For instance, the enzymes for histidine synthesis are in a sequence which corresponds to the linear gene sequence in the histidine operon of Salmonella typhimurium. There is a 20 min period between the appearance of the first and last (tenth) enzymes. The data can be explained on the basis of the successive synthesis of individual mRNA s or on the successive synthesis of a polycistronic message. This... 

They found that the enzymes are derepressed (histidine synthesis begins) in a time sequence corresponding to the linear sequence of the genes in the histidine operon. About 20 minutes... 

It must be pointed out, however, that some metabolic systems have now been studied with feedback inhibition by the end product, in which the end product reacts directly with the enzyme of the first reaction and inhibits it (Datta et al., 1964 Kennell and Magasanik, 1964 Nierlich and Magasanik, 1965). It has been shown in the case of histidine synthesis that the inhibitor of synthesis is not free histidine, but the compound his tidinyl-sRNA, i,e, a more direct product for incorporation into protein synthesis (Schlesinger and Magasanik, 1964). During valine biosynthesis by... 

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