Histidine deficiency

The Ames test involves the reversion from a his— to his+ phenotype in any one of multiple bacterial strains (usually five strains are tested simultaneously). If the addition of test compound to a his— strain of bacteria allows them to grow on histidine deficient media, the obvious conclusion is compound-induced mutagenesis and a high potential hazard for the compound being carcinogenic. This test can also be conducted in the presence or absence of metabolic activation, in order to provide more information on potential risks (i.e., the parent compound may not be mutagenic, but the primary metabolite may present a safety risk). In practice, a positive Ames test almost always leads to discontinuing work on a compound of interest, and so these data are always collected prior to nomination of a compound for development. 

Bothwell, J. W. and Williams, J. N., Jr., A study of histidine deficiency and nitrogen balance under ad libitum and force-feeding conditions, ]. Nutr., 45, 245,1951. 

Forbes, R. M. and Vaughan, L., Nitrogen balance of young albino rats force-fed methionine- or histidine-deficient diet,. Nutr., 52, 25, 1954. 

In an early study (43), mice were kept on a histidine deficient diet supplemented with [2- C] histidine for a red blood cell... 

The bacteria-reversed mutation test is another method to investigate the mutagenic and teratogenic effect of chemicals. This uses numerous amino acid-dependent strains of Salmonella enterica (formerly S. typhimurium). The histidine-dependent strain of S. enterica has artificially induced point mutations. The test is carried out in a histidine-deficient bacterial medium. The histidine-independent bacterial... 

The histidase reaction probably is not reversible. This is supported by the lack of effect of urocanic acid on growth. It has been reported to have no growth-promoting effect on the rat, or only a slight effect on diets deficient in histidine. Feeding or injecting of urocanic acid was unable to check the loss of weight on a histidine-deficient diet. ... 

It is usually assumed that the histidine operon is transcribed into one molecule of messenger RNA, which is then transcribed by the polyribosome system from one end to the other. The histidine operon and corresponding mRNA consist of about 13,000 nucleotides. The possibility that such a polycistronic histidine messenger RNA exists was demonstrated by the work of Martin (1963). The RNA fraction, labeling of which took place differently in histidine-constitutive and histidine-deficient strains, had a sedimentation... 

Hydrolysis of carnosine to p-alanine and L-histidine is catalyzed by carnosinase. The heritable disorder carnosinase deficiency is characterized by carnosinuria. 

Dere, E., Souza-Silva, M. A., Topic, B., Spieler, R. E., Haas, H. L. and Huston, J. P. Histidine-decarboxylase knockout mice show deficient nonreinforced episodic object memory, improved negatively reinforced water-maze performance, and increased neo- and ventro-striatal dopamine turnover. Learn. Mem. 10 510-519, 2003. 

The amino acid histidine is used for the treatment of copper overload in Wilson s disease and forms a strong 1 2 complex (Fig. 27) (553). Copper-histidine therapy is also an efficient treatment for copper deficiency in Menkes disease (554). 

Ghosh AK, Hirasawa N, Ohtsu H, Watanabe T, Ohuchi K Defective angiogenesis in the inflammatory granulation tissue in histidine decarboxylase-deficient mice but not in mast cell-deficient mice. J Exp Med 2002 195 973-982. 

This general approach has, however, serious limitations. The position of the site for attack (and therefore the electron transfer distance involved) is very conjectural. In addition, the vexing possibility, which we have encountered several times, of a dead-end mechanism (Sec. 1.6.4) is always present. One way to circumvent this difficulty, is to bind a metal complex to the protein at a specific site, with a known (usually crystallographic) relationship to the metal site. The strategy then is to create a metastable state, which can only be alleviated by a discernable electron transfer between the labelled and natural site. It is important to establish that the modification does not radically alter the structure of the protein. A favorite technique is to attach (NH3)5Ru to a histidine imidazole near the surface of a protein. Exposure of this modified protein to a deficiency of a powerful reducing agent, will give a eon-current (partial) reduction of the ruthenium(III) and the site metal ion e.g. iron(III) heme in cytochrome c... 

Lactobacillus delbrueckii. In 1953, Rodwell suggested that the histidine decarboxylase of Lactobacillus 30a was not dependent upon pyridoxal phosphate (11). Rodwell based his suggestion upon the fact that the organism lost its ability to decarboxylate ornithine but retained high histidine decarboxylase activity when grown in media deficient in pyridoxine. It was not until 1965 that E. E. Snell and coworkers (12) isolated the enzyme and showed that it was, indeed, free of pyridoxal phosphate. Further advances in characterization of the enzyme were made by Riley and Snell (13) and Recsei and Snell (14) who demonstrated the existence of a pyruvoyl residue and the participation of the pyruvoyl residue in histidine catalysis by forming a Schiff base intermediate in a manner similar to pyridoxal phosphate dependent enzymes. Recent studies by Hackert et al. (15) established the subunit structure of the enzyme which is similar to the subunit structure of a pyruvoyl decarboxylase of a Micrococcus species (16). 

Four Salmonella typhimurium strains, namely TA 98, TA 100, TA 1535 and TA 1538 were used. The TA 100 strain for example bears the his G 46 missense mutation, is excision-repair deficient (uvrB) and has enhanced permeability (rfa). Efficiency of reversion to histidine prototrophy was measured in each case by subtracting the background (ca. 140 spontaneous revertants) from plate counts. 

It plays a vital role in various intracellular reactions e.g. conversion of serine to glycine, synthesis of thymidylate, synthesis of purines, histidine metabolism etc. Due to folic acid deficiency these reactions are affected. 

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