Histidine biosynthesis

The detailed biosynthetic route for histidine in plants is presently undefined incorporation patterns and a very limited amount of enzyme studies indicate that the bacterial pathway is probably used. 

Histidine alone, however, is not capable of reversing the growth effects of amitrole on green plants nucleotide bases are more effective. Purine biosynthesis has been suggested as a more important site of action than IGP dehydratase.Since histidine is ultimately biosynthesized from a purine nucleotide, adenosine triphosphate, the inhibition of histidine formation may only be indirect. Amitrole causes the bleaching of newly formed plant tissue, and pigment biosynthesis has been suggested as an alternative site of herbicide action.Effects of 1,2,4-triazole on cysteine biosynthesis have been noted in bacteria, but no studies have been carried out on plants to assess the relevance of this to amitrole-phytotoxicity.  

Candida yeast species. At the molecular level, amitrole stimulates the transcription of the arom gene in Saccharomyces cerevisiae, probably as a cross-pathway response to histidine starvation.  

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Imidazole-4-catbonitrile, 5-amino-synthesis, 5, 463 Imidazolecarboxamide, cyano-reactions, 5, 436 Imidazole-4-carboxamide Hofmann reaction, 5, 435 Imidazole-4-carboxamide, 5-amino-in histidine biosynthesis, 1, 90 reactions... 

Yeast histidine biosynthesis HIS2 E. coll histidine biosynthesis HIS2 E. coll histidine biosynthesis HIS10... 

Genetic Make up of Tester Strains. The most widely used strains are those developed by Bruce Ames and colleagues which are mutant derivatives of the organism Salmonella typhimurium. Each strain carries one of a number of mutations in the operon coding for histidine biosynthesis. In each case the mutation can be reverted either by base-change or by frameshift mutations. The genotype of the commonly used strains is shown in Table 6.6. 

Wycisk, K., Kim, E. J., Schroeder, J. I., and Kramer, U., 2004, Enhancing the first enzymatic step in the histidine biosynthesis pathway increases the free histidine pool and nickel tolerance mArabidopsis thaliana, FEBS Lett. 578 128-134. 

Histidine Biosynthesis Uses Precursors of Purine Biosynthesis... 

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. 

Many proteins have structures related to those of aminoacyl-tRNA synthetases.282 283 For example, asparagine synthetase A functions via an aspartyl-adenylate intermediate (Chapter 24, Section B), and its structure resembls that of aspartyl-tRNA synthetase.284 The his G gene of histidine biosynthesis (Fig. 25-13) encodes an ATP phosphoribosyltransferase with structural homology to the catalytic domain of histidyl-tRNA synthetase.284 The reason is not clear, but some aminoacyl-tRNA synthetases, especially the histidyl-tRNA synthetase, are common autoantigens for the inflammatory disease polymyosititis.285 286... 

Explain how histidine biosynthesis is controlled in E. coli, a bacterium that has no his repressor. 

The biosynthesis of histidine. The 5-aminoimidazole-4-carboxamide ribotide formed during the course of histidine biosynthesis is also an intermediate in purine nucleotide biosynthesis. Therefore it can be readily regenerated to an ATP, thus replenishing the ATP consumed in the first step in the histidine biosynthetic pathway (see fig. 23.13). 

The earliest currently discernible ancestor in the histidine biosynthesis pathway was a (j8a)4-half-barrel protein which gene-duplicated into two initially identical half-barrels which fused to form an ancestral a/j8-barrel protein. The second gene duplication step led to diversification into two enzymes with distinct catalytic activities. 

Ames Test The Ames test, developed by Bruce Ames and his coworkers at the University of California, Berkeley, depends on the ability of mutagenic chemicals to bring about reverse mutations in Salmonella typhimurium strains that have defects in the histidine biosynthesis pathway. These strains will not grow in the absence of histidine but can be caused to mutate back to the wild type, which can synthesize histidine and hence can grow in its absence. The postmitochondrial supernatant (S-9 fraction), obtained from homogenates of livers of rats previously treated with PCBs in order to induce certain cytochrome P450 isoforms, is also included in order to provide the activating enzymes involved in the production of the potent electrophiles often involved in the toxicity of chemicals to animals. 

Toxic affects of 2-fluoro-L-histidine (2-FHis) (98) on bacteria have been attributed in part to the action of this analogue as a potent feed back inhibitor of ATPiphosphoribo-syl transferase, the first committed enzyme in histidine biosynthesis. No other halogenated analogues of histidine were active in this regard155. 

Scheme 14.4. Substrate specificities of ProFARI (involved in histidine biosynthesis) and PRAI (involved in tryptophan biosynthesis).

These results suggest that MJ0955 is a hisC and prohahly performs the annotated role in histidine biosynthesis. Thus, the identity of the threonine-phosphate decarboxylase remains to be determined. The possible involvement of a pyruvoyl-dependent enzyme in catalyzing this reaction should be considered. 

Histidine biosynthesis in E. coli proceeds in 10 steps that are catalyzed by eight enzymes, three of which are bifunctional. The protein encoded by the HisH gene shares considerable sequence similarity to the giutaminase subunit of CPS, but this enzyme exhibits giutaminase activity only in the presence of a second protein encoded by Biochemical experiments have shown that the HisH/HisF heterodimer (IGP synthase)... 

See also Table 5.1, Genetic Code, Metabolism of Aromatic Amino Acids and Histidine, Biosynthesis of Histidine / Ames Test, Essential Amino Acids... 

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