Histidine operon derepression

Fig. 4. Patterns of derepression of the histidine operon, redrawn from Marver et al. [77]. Histidine was made growth-limiting at time zero. A, simultaneous derepiession B, sequential derepression C, sequential derepression in the presence of ribosyl-AIC of a deletion mutant lacking parts of the hisB and hisH genes.

Goldberger and Berberich (1965) carried out some interesting work to determine the time sequence of activity of the cistrons of the histidine operon based on the kinetics of repression and derepression of five (of the ten) enzymes of this operon from the beginning, middle, and end regions of the histidine operon of S. typhimurium. The specific activity of these enzymes was measured during a period soon before and after removal of histidine from the growth medium of the "leaky" mutant of this microorganism. 

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... 

Another control over termination that has been extensively studied is the attenuation of transcription at the end of the leader regions of several amino acid biosynthetic operons (or genes) in E. coVl and related organisms (39). The primary indication that such a mechanism is involved in the control of an amino acid biosynthetic pathway is an endproduct repression that is dependent on the amino acid being transferred to its cognate tRNA at an ample rate. Thus, derepression of the histidine biosynthetic pathway can be achieved by any mechanism that reduces the intracellular level of histidyl tRNA, for example, by limiting the supply of histidine itself or by limiting the activity of the histidyl tRNA synthetase (51). 

As in the case for derepression, two kinetic patterns for repression of the histidine enzymes have been observed by Goldberger and his colleagues [79]. Unlike the situation for derepression, however, the mode of repression is not related to the formylating capacity of the cell. Instead, the pattern of repression depends on the condition of the feedback site of the first enzyme in histidine biosynthesis, the PR-ATP synthetase [79,80]. When the feedback site is able to function properly, repression is sequential, with the time of repression for eaeh enzyme reflecting the position of its gene in the operon. When the affinity of the feedback site of the PR-ATP synthetase for histidine is reduced, either by mutation or by the addition of a histidine analog which binds to the feedback site, synthesis of all the histidine enzymes ceases simultaneously [79]. 

The finding that a decrease in the level of tRNA" in the cell causes derepression of the operon complements the data from studies of hisS mutants tRNA" is certainly involved in the repression mechanism. However, in the cell tRNA" exists in two forms— one acylated with histidine and the other free. Either of these species could act in the repression process. Since the pool size of acylated tRNA" reflects the... 

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). 

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