Histidine pathway

FIGURE 18-26 Catabolic pathways for arginine, histidine, glutamate, glutamine, and proline. These amino acids are converted to a-ketoglutarate. The numbered steps in the histidine pathway are catalyzed by histidine ammonia lyase, urocanate hydratase, imida-zolonepropionase, and glutamate formimino transferase. 

Analogs and Inhibitors, When we use prototrophic microorganisms, production of repressors can be reduced by addition of end product analogs to the medium. Thus, all 10 histidine pathway enzymes are derepressed up to 30-fold by 2-thiazolealanine (Ames and Hartman, 1963). In a similar manner, adenine, which inhibits thiamine synthesis, derepresses the enzymes of thiamine biosynthesis (Kawasaki et al., 1969). 

Evidence for the presence of the enzymes of the histidine pathway in plants appears to be limited to the work of Winter et al. (1971a) who demonstrated the presence of ATP-phosphoribosyltransferase, the first enzyme of the pathway, imidazole glycerolphosphate dehydratase and histidinol phosphatase in extracts from the shoots of barley, oats, and peas, and to the unpublished observations of Davies (see Davies, 1971) on the presence of histidinol dehydrogenase in rose tissue culture cells. The specific activity of ATP-phosphoribosyltransferase was greatest in peas and oats and least in barley. The enzymes from oats and barley were thermolabile losing activity after 30 min at 37°C. The specific activities of imidazole glycerolphosphate dehydratase were very low but it was possible to purify the enzyme to some extent. The values for imidazole glycerolphosphate for the barley enzyme was 0.6 mM which compares with values for jthe yeast and bacterial enzymes of 0.3 and 0.4 mM, respectively. Histidinolphosphatase was purified 20-fold but the authors considered that two phosphatases were still present. 

The his4 region of yeast [11], and the equivalent genes in Neurospora [13,66-68) and Aspergillus [69], specify three of the enzymic activities in the histidine pathway, the second, third, and tenth steps (Fig. 9). The... 

By definition, during balanced growth all enzymes in the histidine pathway must be operating at the same rate—the rate at which histidine is being assimilated by the cell. It is interesting to compare the activities of the various enzymes with the rate of histidine utiliration. 

The number of nucleotides required to specify the enzymes of the histidine pathway agrees closely with the estimated size of the histidine messenger. This correlation implies that there are no large stretches of untranslated nucleotides between adjacent cistrons of the operon. From the possible error in the estimates of the operon size, an upper limit of about 2000 nucleotides can be set for the combined total of intercistronic nucleotides. 

When formation of PR-AIC via the histidine pathway is prevented by mutation, exogenous ribosyl-AIC may be added to change the... 

Studies of mutation in the histidine pathway of 5. typhimurium have revealed another interesting relationship between genes and operon—coordinate repression. When the wild type of S. typhimurium is grown in a medium containing histidine, the activities of the enzymes involved in histidine biosynthesis are depressed. The activities of all enzymes are depressed equally so that in the mutant, the ratio of the activity of one enzyme to that of another enzyme is the same as in the wild type. To explain coordinated repression it is proposed that the entire base sequence in the operon is translated into a single molecule of messenger RNA. 

The observations on the histidine operons described above clearly show that all the enzymes with amino acid sequences determined by the histidine operon are not synthesized in equimolecular amounts. But the rate at which each of the proteins is synthesized is determined by the position of the cistron within the operon. The amount of protein synthesized decreases the further the cistron is from the operator gene. Furthermore, mutations that interfere with the biosynthesis of one enzyme of the histidine pathway lead to a reduction of the rate of synthesis of all the enzymes with structures dictated by cistrons distal to the mutated cistron. 

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