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)

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

Depletion of circulating L-asparagine has proved beneficial in the treatment of some acute lymphoyctic leukemias. To avoid the immunologic sequelae of administering L-asparaginase parenterally, we have covalently attached the enzyme to the outside of the fibers of a conventional hollow fiber hemodialyzer. This provides ready access of the substrate to the enzyme, while simultaneously isolating the foreign protein from the immune system. Such reactor-dialyzers perform well, both in vitro and in vivo. Circulating L-asparagine in the healthy dog is reduced from about 50 micrometer to less than 2 micrometer within 30 min of connecting the reactor-dialyzer and the reduction persists for at least 4 hr after cessation of treatment.
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PMID:A new extracorporeal reactor-dialyzer for enzyme therapy using immobilized L-asparaginase. 43 2

The effect of L-glutamine and L-asparagine depletion by Acinetobacter L-glutaminase-L-asparaginase on the toxicity and antitumor activity of L-(alphaS,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid (NSC-163501) was tested in mice. The LD50 of six daily doses of NSC-163501 in BDF1 female mice decreased from 7.5 to 0.3 mg/kg/day by combination treatment with the enzyme. Enzyme therapy also decreased the dose of NSC-163501 needed for maximal prolongation of survival in these mice inoculated with L1210 leukemia. Nevertheless, the combination did not prolong survival in L1210-bearing mice beyond that of higher doses of NSC-163501 alone. In contrast, the combination of enzyme plus NSC-163501 inhibited the growth of established sc implanted Ehrlich ascites carcinoma in ICRf male mice much more than either agent alone. Treatment with Acinetobacter L-glutaminase-L-asparaginase decreased the L-asparagine and L-glutamine levels in acid extracts of the Ehrlich tumor. NSC-163501 did not affect the amide levels or alter the decrease produced by enzyme therapy.
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PMID:Enhanced effect of an L-glutamine antagonist, L-(alphaS,5S)-alpha-amino-3-chloro-4,5-dihydro-5-isoxazoleacetic acid, by Acinetobacter L-glutaminase-L-asparaginase. 46 50

L-Asparaginase was immobilized in spherical microparticles of polyacrylamide. Particles of three different sizes, mean diameter 0.34, 18 and 36 micron, respectively, were used. The Michaelis constant Km, for L-asparaginase, immobilized in small particles (0.34 micron), is virtually the same as in solution. L-Asparaginase in microparticles was also more stable than free enzyme after storage for 140 days at +4 and +37 degrees C. After an i.v. injection of 200 I.U./kg into rat, the plasma L-asparagine fell to very low values (less than 10 nmol/ml), but was normalized again after 4 to 5 days with both the native and immobilized enzymes. After an i.p. injection of 1000 I.U./kg into rats, the microparticles containing L-asparaginase lowered the plasma L-asparagine level for a substantially longer period of time than L-asparaginase in free solution. Normal L-asparagine level was thus reached on day 14 after the injection with immobilized enzyme. However, L-asparaginase activity was still present in the abdominal lymph nodes after this period of time.
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PMID:Acrylic microspheres in vivo. II. The effect in rat of L-asparaginase given in microparticles of polyacrylamide. 51 28

Three human isolates of Vibrio succinogenes produced asparaginase. Apparent Km's were 87,220, and 320 microM. The rate of glutamine hydrolysis was between 2.8 and 3.5% of the rate of asparagine hydrolysis. Asparaginase production was not induced by ammonium ions, and enzyme yields were lower than those obtained with the rumen strain.
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PMID:Asparaginase production by human clinical isolates of Vibrio succinogenes. 53 25

L-Asparaginase sensitivity and asparagin-deficiency of 5 tumor cell populations, i.e. mouse lymphoma L-1210, LI0-1, LTL, Berkitt lymphoma and human ovary cancer, line CaOv were studied. Radiometric estimation of 3H-thimidine incorporation into the cells of DNA served a criterion of cytotoxicity. "Krasnitin" (FDR) was used as L-asparaginase. The cells of leukemia L-1210, lymphosarcoma LIO-1 and line CaOv were asparagine-independent and non-sensitive to L-asparaginase. The cells of mouse lympholeukemia LTL and the cultures of Berkitt human lymphoma proved to be asparagin-dependent and highly sensitive to L-asparaginase. In concentration of 50 IU/ml the drug inhibited incorporation of 3H-thimidine in the cells of LTL and Berkitt lymphoma by 97-98 and 75-80 per cent respectively. Inhibition of 3H-thimidine incorporation in the cells of LTL and Berkitt lymphoma was more pronounced after incubation with the drug for 8 and 24 hours respectively. Two out of the 5 tumor cell populations were chosen as a result of the study. One of these 2 populations, i.e. the cells of Berkitt lymphoma was asparagin-dependent and highly sensitive to L-asparaginase, the other, i.e. the cells of line CaOv was asparagin-independent and resistant to the specific antitumor effect of the enzyme. The use of a system of these two cell lines provided estimation of the ratio of the specific cytostatic (antitumor activity) and non-specific cytostatic properties in the preparations with L-asparaginase activity.
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PMID:[Cellular test system for studying the biological properties of preparations with L-asparaginase activity]. 59 48

Since asparagine has been found to inhibit growth of some tumors and to inhibit or delay mitotic activity in other cells, we have studied the effect of asparaginase and of deprivation of some essential amino acids (Arg, Asn, Leu, Ile, Trp) on nucleic acid and protein synthesis in an asparagine-requiring strain of BHK/21 cells. We find that: (1) there is no essential difference in the pattern of synthesis following deprivation of any of the amino acids we tested; (2) that the effect of asparaginase is similar to that of amino acid deprivation; (3) that RNA synthesis is inhibited more rapidly than DNA or protein synthesis; (4) that after 10 hr of amino acid starvation, DNA synthesis is almost totally (reversibly) inhibited while RAN synthesis continues at about 30-50% and protein at about 100% of the initial value.
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PMID:The effect on macromolecular synthesis of amino acid deprivation of hamster kidney cells. 61 19

The activity of deamidases of L-glutamine and L-asparagine of Pseudomonas boreopolis 526 was found to depend on the conditions of cultivation. The activity of L-glutaminase-asparaginase II (EC 3.5.1.38) decreased with an increase of the specific growth rate in the conditions of periodic cultivation and increased in the conditions of continuous cultivation. The activity of this enzyme was manifested mainly in the conditions of continuous cultivation at a rate of 0.1--0.2 hr-1 and a final nitrogen concentration of 0.006--0.025 g per litre of the medium. If the concentration of nitrogen was increased in these conditions, biosynthesis of L-glutaminase-asparaginase I was stimulated while the activity of L-glutaminase-asparaginase II was not detected at all.
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PMID:[L-glutaminase-asparaginase biosynthesis by a Pseudomonas boreopolis culture dependent on cultivation conditions]. 67 79

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

Cell extracts of Bacillus polymyxa var. Ross.--producer of the polypeptide antibiotic polymyxin M. showed activity of L-asparaginase-2 (L-asparagine aminohydrolase EC 3.5.1.1). The enzyme activity in the growing culture increased with the biomass. The highest specific activity was detected in the cells at the onset of the stationary stage. The synthesis of L-asparaginase-2 was subjected to glucose catabolite repression in response to its addition to the culture at the logarithmic stage. After purification L-asparaginase-2 was obtained that was 350 times more active than the initial preparation. The enzyme properties were examined.
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PMID:[Biosynthesis of L-asparaginase-2 by cultures of Bacillus polymyxa var. Ross]. 72 59


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