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

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

The role of amino acids in regulation of L-asparaginase formation was studied in Bacillus mesentericus 43A. Asparagic acid and, to a less extent, asparagine repress biosynthesis of the enzyme. Glutamic acid, glutamine, and other 15 studied amino acids, added separately at a concentration of 10 or 20 mM to the growing culture, have no effect on the activity of the enzyme. Addition of a combination of all 18 amino acids, each at a concentration of 4 mM, to the culture represses the activity by 64%; addition of an acid hydrolysate of lactoalbumin (10 g/litre) represses the activity of the enzyme by 80%. A mixture of amino acids without asparagic acid and asparagine also displays a strong repressing action. Amino acids formed from asparagic acid--lysine, methionine, and isoleucine--do not repress biosynthesis of the enzyme, neither together nor separately. Ammonium nitrogen also does not participate in regulation of asparaginase formation. The cumulative repressing action of amino acids is supposed to be manifested via the mechanism of catabolite repression.
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PMID:[Amino acid regulation of L-asparaginase formation in Bacillus mesentericus]. 93 71

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 was used to replace the three histidine residues of Escherichia coli asparaginase II (EcA2) with other amino acids. The following enzyme variants were studied: [H87A]EcA2, [H87L]EcA2, [H87K]EcA2, [H183L]EcA2 and [H197L]EcA2. None of the mutations substantially affected the Km for L-aspartic acid beta-hydroxamate or impaired aspartate binding. The relative activities towards L-Asn, L-Gln, and l-aspartic acid beta-hydroxamate were reduced to the same extent, with residual activities exceeding 10% of the wild-type values. These data do not support a number of previous reports suggesting that histidine residues are essential for catalysis. Spectroscopic characterization of the modified enzymes allowed the unequivocal assignment of the histidine resonances in 1H-NMR spectra of asparaginase II. A histidine signal previously shown to disappear upon aspartate binding is due to His183, not to the highly conserved His87. The fact that [H183L]EcA2 has normal activity but greatly reduced stability in the presence of urea suggests that His183 is important for the stabilization of the native asparaginase tetramer. 1H-NMR and fluorescence spectroscopy indicate that His87 is located in the interior of the protein, possibly adjacent to the active site.
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PMID:Site-specific mutagenesis of Escherichia coli asparaginase II. None of the three histidine residues is required for catalysis. 152 38

L-Asparaginase of T. pyriformis is a membrane-bound enzyme with an active site situated on the outside surface of the membrane. When radioactive L-asparagine was incubated with T. pyriformis cells in the L-asparaginase assay medium, the hydrolysis was 240 higher than the uptake of this amino acid. In a similar experiment performed in salt medium (Wagner's solution), the hydrolysis was linearly increased and reached after one hour of incubation a value of 60 nmol/10(6) cells, while the uptake after 20 min of incubation reached a plateau with a value of 15 nmol/10(6) cells. The uptake of L-leucine under these conditions was 44 nmol/10(6) cells/hr, while no measurable transport of aspartic acid was observed. That L-aspartic acid is not migrated into T. pyriformis cells is in agreement with the finding that no efflux of this amino acid takes place as well. The uptake of L-asparagine is pH and K+ dependent, whereas Na+ ions strongly inhibit this uptake. The Km and Vmax values of L-asparagine uptake is 1.43 mM and 0.7 nmol/min, respectively. The half life of L-asparagine "protein transport system" was 40 min, a value which is very close to the half life of the membrane-bound L-asparaginase of this microorganism. Ouabain and vanadate inhibit the uptake of L-asparagine by more than 80%, while ouabain or vanadate inhibit in vivo 5% or 95% the activity of L-asparaginase, respectively. This indicates the lack of interrelationship between the L-asparagine "protein transport system" and the L-asparaginase protein molecule.
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PMID:Transport of L-asparagine in Tetrahymena pyriformis ecto-L-asparaginase is not related to L-asparagine-protein transport system. 193 Feb 47

In June 1984, the Pediatric Oncology Group (POG) initiated a pilot study (8498) using high-dose cytarabine (HdA; 3 g/m2) for intensification of early therapy in childhood acute myelogenous leukemia (AML) (group I). Remission induction therapy consisted of two courses of daunorubicin, cytarabine (Ara-C), and thioguanine (DAT). Postremission therapy consisted of four sequential courses, each consisting of (1) four doses of HdA (HdA4) followed by asparaginase (L-Asp), (2) etoposide (VP) plus azacytidine (Az), (3) prednisone, vincristine, methotrexate, and mercaptopurine (POMP), and (4) Ara-C daily for 5 days by continuous infusion. Six doses of intrathecal Ara-C were given for CNS prophylaxis. In December 1986, the protocol was amended (group II) to substitute six doses of HdA (HdA6) for the second DAT (two + five) induction course; postinduction, a single course of HdA6 was given instead of four HdA/L-Asp courses, and the remainder of the therapy was unchanged. One hundred forty group I patients and 145 group II patients were assessable. The two groups were similar with regard to clinical prognostic groups. No significant differences were noted in the two groups with regard to remission induction (85% [SE = 2%] in each group), induction deaths (6.5% v 7.0%), or deaths in remission (one in each group). Cerebellar toxicity was reported in three patients in group II (with HdA6) but none in group I (HdA4). At present, patients who received HdA6 (group II) had higher event-free survival than patients in group I (EFS at 3 years, 34% [SE = 11%] v 29% [SE = 4%]), and disease-free survival (DFS at 3 years, 42% [SE = 14%] v 34% [SE = 4%]), but the differences were not statistically significant. In both groups, children less than 2 years and those with WBCs less than 100,000/microL had significantly better outcome (EFS of 55% [SE = 10%] and 36% [SE = 5%] at 3 years, respectively) than children greater than or equal to 2 years and those with WBCs greater than or equal to 100,000/microL (EFS of 27% [SE = 5%] and 20% [SE = 9%] at 3 years, respectively.
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PMID:High-dose cytarabine for intensification of early therapy of childhood acute myeloid leukemia: a Pediatric Oncology Group study. 206 54


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