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

L-asparaginase pretreatment prior to sublethal whole body irradiation resulted in decrease of endogenous spleen colonies. This effect was abolished by the simultaneous addition of L-asparagine. L-asparaginase administered after sublethal irradiation did not reduce the number of spleen colonies. This result agrees with the suggestion that L-asparaginase inhibits the proliferation of undifferentiated but not of differentiated cells.
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PMID:Influence of L-asparaginase on spleen colony formation in mice. 74 22

Yeast strains sigma1278b and Harden and Young, which synthesize only an internal constitutive form of L-asparaginase, do not grow on D-asparagine, as a sole source of nitrogen, and whole cell suspensions of these strains do not hydrolyze D-asparagine. Strains X2180-A2 and D273-10B, which possess an externally active form of asparaginase, are able to grow slowly on D-asparagine, and nitrogen-starved suspensions of these strains exhibit high activity toward the D-isomer. Nitrogen starvation of strain X218O-A2 results in coordinate increase of D- and L-asparaginase activity; the specific activity observed for the D-isomer is approximately 20% greater than that observed for the L-isomer. It was observed, in studies with cell extracts, that hydrolysis of D-asparagine occurred only with extracts from nitrogen-starved cells of strains that synthesize the external form of asparaginase. Furthermore, the activity of the extracts toward the D-isomer was always higher than that observed with the L-isomer. A 400-fold purified preparation of external asparaginase from Saccharomyces cerevisiae X218U-A2 hydrolyzed D-asparagine with an apparent Km of 0.23 mM and a Vmax of 38.7 mumol/min per mg of protein. D-Asparagine was a competitive inhibitor of L-asparagine hydrolysis and the Ki determined for this inhibition was approximately equal to its Km. These data suggest that D-asparagine is a good substrate for the external yeast asparaginase but is a poor substrate for the internal enzyme.
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PMID:Utilization of D-asparagine by Saccharomyces cerevisiae. 76 32

Among studied 40 bacterial cultures, 17 strains catalysed hydroxylaminolysis of I.-asparagine and L-glutamine, and among these cultures seven strains belonged to the Pseudomonas genus. Extracts of the cells of Ps. boreopolis 526 (MGU), Ps. aurantiaca IBFM B-14, and Ps. septica IBFM B-40 had the maximum deamidase activity during the stage of decelerated growth. The activity of L-asparaginase 2 was practically the same upon various ways of disintegration of the cells of Ps. aurantiaca IBFM B-14: ballistic technique, ultrasound, extrusion form the solid state. Production of beta-aspartylhydroxamic acid by L-asparaginase 2 depended on the concentration of hydroxylamine and protein in the reaction mixture and on the duration of the reaction.
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PMID:[Formation of L-asparagine and L-glutamine deamidases by bacterial cultures]. 78 74

The relative antineoplastic effectiveness of E. coli and Erwinia asparaginases was tested against lymphoid leukemias EARAD-1 and L5178Y/CA55. E. coli and Erwinia asparaginases had similar clearance rates from plasma in mice, and at a dose of 250 IU/kg body weight both enzymes lowered plasma asparagine to undetectable levels. Nevertheless, the dosage of Erwinia asparaginase needed to cause similar prolongation of median survival time in leukemic mice was at least twice that of E. coli asparaginase. The factors which may be responsible for the more potent therapeutic effectiveness of the E. coli asparaginase are discussed.
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PMID:A comparative study of the antitumor effectiveness of E. coli and Erwinia asparaginases. 78 92

The effect of pretreatment with L-asparaginase on the cytotoxicity of methotrexate (MTX) was studied in L5178Y murine leukemic cells and L-929 cells grown in vitro. The results were correlated with the effects of L-asparaginase on DNA synthesis. At low concentrations of the enzyme, pretreatment of cells enhanced the effect of MTX; at higher concentrations, it prevented the effect of MTX. Elimination of the MTX action was demonstrated also in L5178Y cells growing in the medium lacking L-asparagine. L-Asparagine readdition resulted in enhancement of MTX cytotoxicity. Pulse-labeling experiments demonstrated that in every case elimination of MTX action was related to a diminution of the fraction of cells in the phase of DNA synthesis. In contrast, enhancement of the effect of MTX was related to an increase in the fraction of cells in the DNA synthesis phase. A similar parallelism of effects occurred in L-929 cells when pretreatment with L-asparaginase was followed by washing the cells and culturing them in medium without the enzyme.
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PMID:Role of amino acid depletion in combined treatment of neoplastic cells with methotrexate and L-asparaginase. 80 60

These results suggest that asparaginase-collagen preparations, with activity and stability values surpassing those reported for other immobilization procedures, can be potentially utilized as an efficient extracorporeal chemptherapeutic device for the treatment of tumors, producing less side effects than the soluble enzyme therapy, for a given level of asparagine clearance.
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PMID:Reduction of canine serum asparagine levels by L -asparaginase immobilized on collagen: a potential form of cancer chemotherapy. 80 12

Short intensive treatment with N-diazoacetylglycine amide (DGA) before the inoculum, followed by prolonged daily administration of L-asparaginase (Asnase), was tested for its ability to elicit tumorigenic properties of fibroblast-like cells cultured in vitro. With this treatment progressive tumor growth was obtained in allogeneic mice injected with cells of a transformed subline. Results show that combined use of DGA and Asnase affords a higher probability of proving in vivo the tumorigenic properties of injected cells than in newborm or X-irradiated recipients. Experimental data indicate that L-asparagine depletion does not inhibit the in vitro growth of fibroblast-like cells.
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PMID:[An effective immunodepressive treatment for demonstrating in allogeneic mice the tumorigenic properties of cells grown in vitro (author's transl)]. 80 86

The cells of Pseudomonas fluorescens AG contain two inducable asparaginase enzymes: one of them hydrolyzes only L-asparagine (asparaginase A), the other--L-asparagine, L-glutamine, and D-asparagine (asparaginase AG). In the conditions of continuous cultivation of the bacteria, aspartic and glutamic acids induce the formation of these enzymes only when the amino acids were used simultaneously as a growth-limiting factor and as a sole source of carbon and nitrogen. Both enzymes are not induced in the conditions when the growth is limited by the nitrogen of these amino acids. When the growth was limited by carbon, asparagine, aspartic and glutamic acids induce asparaginase AG more than asparaginase A. Asparagine and glutamine are better inductors than the corresponding amino acids. The activity of asparaginase and glutaminase increases with the specific growth rate of the culture. The induced synthesis of both amidases, after prolonged growth of the culture on a defined medium with glycerol, is inhibited by glycerol but not by glucose. The results are discussed from the viewpoint of regulation of amidases in these bacterial cells.
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PMID:[Asparaginase and glutaminase activity in Pseudomonas fluorescens in continuous cultivation]. 80 40

An enzyme that catalyzes the hydrolysis of both glutamine and asparagine has been purified to homogeneity from extracts of Pseudomonas acidovorans. The enzyme having a ratio of glutaminase to asparaginase of 1.45:1.0 can be purified by a relatively simple procedure and is stable upon storage. The glutaminase-asparaginase has a relatively high affinity for L-asparagine (Km=1.5 X 10(-5) M) and L-glutamine (Km=2.2 X 10(-5) M) and has a molecular weight of approximately 156,000 the subunit molecular weight being approximately 39,000. Injections of the enzyme produced only slight increases in the survival time of C3H/HE mice carrying the asparagine-requiring 6C2HED Gardner lymphoma and of white Swiss mice carrying the glutamine-requiring Ehrlich lymphoma.
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PMID:Purification and properties of L-glutaminase-L-asparaginase from Pseudomonas acidovorans. 84 19

This paper is concerned with the evaluation of the in vivo performance characteristics of reconstituted bovine collagen as an insoluble carrier matrix fro therapeutic enzymes. The enzyme that was chosen as a model for this evaluation was E. coli L-asparaginase, which has been widely investigated as a soluble chemotherapeutic agent for the treatment of acute lymphocytic leukemia in humans (Oettgen et al., Cancer Res., 27, 2619, 1967 ; Beard et al., Brit. Med. J., 1, 191, 1970; Ohmuma et al., Cancer Res., 30, 2297, 1970). The results presented here were obtained from perfusion trials with a collagen-asparaginase reactor incorporated into an extracorporeal circuit attached to the vascular systems of healthy mongrel dogs. A series of 1-2 hr perfusions were conducted with a single collagen-asparaginase membrane over a period of 4 months. Serum asparagine levels were reduced by more than 98% after 15-30 min perfusion time. Red blood cell (RBC), hemoglobin, hematocrit, and fibrinogen values remained constant during each perfusion. An average decrease of 48% in white blood cell (WBC) and 24% in platelet levels was observed, but these values began to rise slowly even before cessation of the perfusion. No serious toxic or antigenic reactions or mechanical or clotting difficulties were observed. In vitro activity, when assayed between perfusions, remained constant over a period of 4 months of intermittent use and storage. The potential advantages of collagen-enzyme complexes for the administration of therapeutic enzymes is discussed.
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PMID:Perfusion trials with a collagen-immobilized enzyme in an extracorporeal reactor: activity, stability, and biocompatibility. 84 82


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