Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.5.1.1 (asparaginase)
 2,695 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cultural and nutritional requirements for a maximum synthesis of 1-asparaginase by staphylococci were determined. The best production of the enzyme was found in the stationary phase of growth of a batch culture. The highest 1-asparaginase yield was obtained when the culture were aerated during an exponential phase of growth and further incubated in the stationary phase. Optimum pH for the enzyme production was 7.5. Glucose inhibited the enzyme formation. Maximum yield of 1-asparaginase was obtained when casein hydrolysate and yeast extract were supplied as carbon and nitrogen sources. Repression by 1-asparagine and 1-aspartic acid was absent.
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PMID:Factors influencing L-asparaginase production by staphylococci. 1 83

The uptake of L-asparagine by Escherichia coli K-12 is characterized by two kinetic components with apparent Km values of 3.5 muM and 80 muM. The 3.5 muM Km system displays a maximum velocity of 1.1 nmol/min per mg of protein, which is a low value when compared with derepressed levels of other amino acid transport systems but is relatively specific for L-asparagine. Compounds providing effective competition for L-asparagine uptake were 4-carbon analogues of the L-isomer with alterations at the beta-amide position, i.e., 5-diazo-4-oxo-L-norvaline (Ki = 4.6 muM), beta-hydroxyamyl-L-aspartic acid (Ki = 10 muM), and L-aspartic acid (Ki = 50 muM). Asparagine uptake is energy dependent and is inhibited by a number of metabolic inhibitors. In a derived strain of E. coli deficient in cytoplasmic asparaginase activity asparagine can be accumulated several-fold above the apparent biosynthetic pool of the amino acid and 100-fold above the external medium. The high affinity system is repressed by culture of cells with L-asparagine supplements in excess of 1 mM and is suggested to be necessary for growth of E. coli asparagine auxotrophs with lower supplement concentrations.
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PMID:L-asparagine uptake in Escherichia coli. 23 25

Saccharomyces cerevisiae X2180-1A synthesizes two forms of asparaginase: L-asparaginase I, an internal constitutive enzyme, and asparaginase II, an external enzyme which is secreted in response to nitrogen starvation. The two enzymes are biochemically and genetically distinct. The structural gene for asparaginase I (asp 1) is closely linked to the trp 4 gene on chromosome IV. The gene controlling the synthesis of asparaginase II is not linked to either the trp 4 or asp 1 genes. The rate of biosynthesis of asparaginase II is unaltered in yeast strains carrying the structural gene mutation for asparaginase I. Asparaginase II has been purified approximately 300-fold from crude extracts of Saccharomyces by heat and pH treatment, ethanol fractionation, ammonium sulfate fractionation followed by Sephadex G-25 chromatography, and DEAE-cellulose chromatography. Multiple activity peaks were obtained which, upon gas chromatographic analysis, exhibit varying mannose to protein ratios. Asparaginase I has been purified approximately 100-fold from crude extracts of Saccharomyces by protamine sulfate treatment, ammonium sulfate fractionation, gel permeation chromatography, and DEAE-cellulose chromatography. No carbohydrate component was observed upon gas chromatographic analysis. Comparative kinetic and analytic studies show the two enzymes have little in common except their ability to hydrolyze L-asparagine to L-aspartic acid and ammonia.
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PMID:Characterization of two forms of asparaginase in Saccharomyces cerevisiae. 34 21

Deamidase AG (asparaginase-glutaminase) from Pseudomonas fluorescens AG was shown to hydrolyze 1-glutamine and 1-asparagine highly effectively. Besides, the enzyme exhibited the rather high rate of deamidation of D-asparagine and D-glutamine (70% and 100%, respectively), Nalpha-butyl asparagine (63%) and among peptides -- of glycyl-L-asparagine (40%). L-glutamic acid gamma-methyl ester was hydrolyzed only slightly (5%). Effect of several substrate analogues on the deamidase AG activity was studied as well. Albiciine (alpha-amino-beta-ureide propionic acid) proved to be the strongest inhibitor (100%). Beta-Methyl aspartic acid, S-carbamoyl cysteine, alpha-ketoglutaric acid showed the slight inhibitory effect (20%). Amount of active centres per enzyme molecule was estimated by means of 14C-albiciine. Deamidase AG had apparently only one active centre. In estimation of relationship between the rate of reaction and substrate (L-asparagine) concentration, the reaction was found to follow Michaelis-Menten kinetics, K(m) = 4.5 with 10-4 M.
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PMID:[Substrate specificity, inhibitors and kinetics of deamidase AG (asparaginase-glutaminase) from Pseudomonas fluorescens AG]. 41 63

Morphine and aspartic acid were administered separately and in combination to 80 rats divided into 8 groups. Ten and 20 min following the injections, brain, liver and kidney L-asparaginase activity was determined. Morphine decreased brain and liver L-asparaginase activity and increased that of kidney. Aspartic acid completely antagonized the effect of morphine. Additionally 500 IU/kg L-asparaginase and 5 or 10 mg/kg morphine were i.v. injected into 56 rats divided into 5 groups. L-Asparaginase, which, in turn, increased motor activity, antagonized the morphine-induced hypoactivity and analgesia. These results support our previous findings.
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PMID:The relationship between morphine, aspartic acid and L-asparaginase in rats. 52 70

Growing cells of Yersinia pseudotuberculosis, but not those of closely related Yersinia pestis, rapidly destroyed exogenous L-aspartic and L-glutamic acids, thus prompting a comparative study of dicarboxylic amino acid catabolism. Rates of amino acid metabolism by resting cells of both species were determined at pH 5.5, 7.0, and 8.5. Regardless of pH, Y. pseudotuberculosis destroyed L-glutamic acid, L-glutamine, L-aspartic acid, and L-asparagine at rates greater than those observed for Y. pestis. Although rates of proline degardation were similar, its metabolism by Y. pestis at pH 8.5 resulted in excretion of glutamic and aspartic acids. Similarly, Y. pestis excreted aspartic acid when incubated with L-glutamic acid (pH 8.5) or L-asparagine (pH 5.5, 7.0, and 8.5). Aspartase activity was not detected in extracts of 10 strains of Y. pestis but was present in all 11 isolates of Y. pseudotuberculosis. The latter contained significantly more glutaminase, asparaginase, and L-glutamate-oxalacetate transminase activity than did extracts of Y. pestis; specific activities of L-glutamate dehydrogenase and alpha-ketoglutarate dehydrogenase were similar. The observed differences in dicarboxylic amino acid metabolism are traceable to asparatase deficiency in Y. pestis and may account for the slow doubling time of this organism relative to Y. pseudotuberculosis.
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PMID:Consequences of aspartase deficiency in Yersinia pestis. 71 77

Biosynthesis of L-asparaginase (EC 3.5.1.1) was inhibited in the growing culture of Bac. mesentericus 43A on addition of L-aspartic acid (20 mM). My treatment with methyl nitrosourea (2 mg/ml) mutants were obtained, which grew poorly on aspartic acid used as the only source of carbon and nitrogen. The aspartic acid did not repress the asparaginase biosynthesis in 8 strains, found between the mutants. In six of these mutants the asparaginase biosynthesis was inhibited by means of the type of catabolite repression. The data obtained suggest that in Bac. mesentericus 43A the asparaginase biosynthesis is controlled more likely by two independent mechanisms: 1) specific repression with aspartic acid as an end product and 2) catabolite repression.
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PMID:[Regulation of L-asparaginase biosynthesis in mutants of Bacillus mesentericus 43A, poorly growing in the presence of aspartic acid]. 102 95

The effect of dietary asparagine on rat growth was investigated. Diets were formulated with L-amino acids so as to contain asparagine, aspartic acid, glutamine and/or glutamic acid in all possible combinations and then fed to weanling rats for 3 weeks. Of the four, only asparagine was found to be essential for optimal growth, and it was essential regardless of the presence or absence of any dietary combination of these related amino acids. In selected dietary groups, the unbound asparagine levels were measured in various tissues over an 8-day period. Muscle asparagine levels were reduced for asparagine-deprived animals over the entire period studied; brain levels were decreased only after 7 days of dietary depletion, while hepatic levels were unaffected by dietary asparagine deprivation. In a related series, animals were more drastically depleted of asparagine by combining dietary deprivation with asparaginase treatment, causing a rapid decrease in cellular concentration of asparagine, which affected protein and DNA synthesis for those organs undergoing hyperplastic growth. Thus, asparagine may be rate limiting to protein synthesis for this extreme case as well as during dietary asparagine deprivation, which also decreased intracellular levels of unbound asparagine and led to irreversible deficits in development.
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PMID:An asparagine requirement in young rats fed the dietary combinations of aspartic acid, glutamine, and glutamic acid. 111 47

Site-specific mutagenesis has been used to probe amino acid residues proposed to be critical in catalysis by Escherichia coli asparaginase II. Thr12 is conserved in all known asparaginases. The catalytic constant of a T12A mutant towards L-aspartic acid beta-hydroxamate was reduced to 0.04% of wild type activity, while its Km and stability against urea denaturation were unchanged. The mutant enzyme T12S exhibited almost normal activity but altered substrate specificity. Replacement of Thr119 with Ala led to a 90% decrease of activity without markedly affecting substrate binding. The mutant enzyme S122A showed normal catalytic function but impaired stability in urea solutions. These data indicate that the hydroxyl group of Thr12 is directly involved in catalysis, probably by favorably interacting with a transition state or intermediate. By contrast, Thr119 and Ser122, both putative target sites of the inactivator DONV, are functionally less important.
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PMID:Probing the role of threonine and serine residues of E. coli asparaginase II by site-specific mutagenesis. 128 59

It has previously been shown that subchronic and acute administration of L-asparaginase and glutaminase inhibitors D-Aspartic acid (D-ASP) and prolyl-leucyl-glycinamide (PLG) intensifies and attenuates morphine (M) physical dependence, respectively, by the inhibition of ASP and glutamic acid (GLU) production, and subsequently their normal releases. Tizanidine (TIZ) has long been known to be an alpha 2-adrenoceptor agonist and inhibitor of ASP and GLU release. Therefore, in this study TIZ has been administered subchronically during the development of M physical dependence to rats in which M-containing pellets had been implanted or acutely 30 min before naloxone (NL)-induced abstinence syndrome. The subchronic administration of TIZ intensified NL-precipitated abstinence syndrome whereas its acute administration attenuated it, as did D-ASP and PLG. On the other hand, TIZ added into the medium prevented the in vitro M-dependent-made guinea pig ileum from contracting following NL application. Furthermore, TIZ stopped the already started contraction by NL of the M-dependent ileum, which completely relaxed later. These effects of TIZ on M-dependent ileum were antagonized by the alpha 2-adrenoceptor antagonist yohimbine. The intensification by subchronic TIZ administration of abstinence syndrome was attributed to the lesser release of ASP and GLU, which resulted in the larger blockade of M of ASPergic/GLUergic receptors due to the lesser release of their endogenous agonist ASP and GLU and consequently the higher upregulation of the receptors. The attenuation by acute TIZ administration of NL-precipitated abstinence syndrome was explained with lesser release of ASP and GLU and concomitantly the lesser stimulation of the receptors.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effects of tizanidine on morphine physical dependence: attenuation and intensification. 135 95


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