Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

The changes in the production of antibody against Salmonella typhimurium antigen were investigated in rats by means of the agglutination test after chronic oral administration of the L-asparaginase inhibitors morphine (M) or D-aspartic acid (D-Asp) alone or together with L-aspartic acid (L-Asp) and food restriction, all of which had been started five days before the injections of antigen. The statistical evaluation, carried out after the titers had been defined as -log2 of the highest dilution giving a positive agglutination reaction, showed that M or D-Asp significantly decreased antibody production in comparison with the immunized control or food restricted group. The concomitant administration of L-Asp appeared to significantly antagonize the inhibitory effect of both M and D-Asp. Therefore, the results were considered as further supporting evidence for the fact that the deleterious effect of M on the immune system and its functions might be related to the inhibitory effect of M on L-asparaginase activity.
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PMID:The inhibition by morphine and D-aspartic acid of antibody production against Salmonella typhimurium antigen in rats: its antagonism by L-aspartic acid. 355 13

The enzyme asparaginase, which hydrolyses asparagine to aspartic acid, inhibited cell-free protein synthesis by reticulocyte lysates. The inhibition was rapid and complete when sufficient enzyme was added but could be prevented or reversed by the addition of asparagine. The initial effect of asparaginase appears to be a block in polypeptide chain elongation due to asparagine deprivation, but there are some indications that prolonged incubation under these conditions may give rise to a secondary decrease in initiation of protein synthesis.
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PMID:Control of protein synthesis by amino acid supply. The effect of asparagine deprivation on the translation of messenger RNA in reticulocyte lysates. 394 Aug 84

In studies on kinetics of thermoinactivation of glutaminase (asparaginase) from Ps. arantiaca BKMB-548 at 50 degrees and pH 7.0 in presence or in absence of L-glutamate the enzyme inactivation was found to obey the first order equation. Both the glutaminase and asparaginase activities decreased at a similar rate. L-Glutamate stabilized the enzyme due to direct interaction with its molecule. Stability of the complex formed was evaluated quantitatively. L-Glutamate reacted apparently with a specific site on the surface of the enzyme molecule; Kdiss was 0.42 +/- 0.03 mM at pH 7.0 and 50 degrees. No cooperative effect was found. L-Aspartate protected the enzyme completely; stabilizing effects of L-cysteine, L-serine and glycine were similar to the effect of L-glutamate (94%, 84%, 83% and 82%, respectively). At the same time, glutarate, succinate, alpha-ketobutyrate, alpha-ketoglutarate, gamma-aminobutyrate and N-benzoyl glutamate did not exhibit the stabilization effect. The data obtained suggest that the high stabilizing effect might exhibit only the substances containing simultaneously free alpha-NH2 and alpha-COOH groups in a molecule, whereas presence of COOH groups at beta--or gamma-carbon atoms was not essential for the stabilizing effect.
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PMID:[Thermostabilization of glutamin(asparagin)ase from Pseudomonas aurantica BKMB-548]. 402 28

Asparagine is able to penetrate into human erythrocytes from the external medium. The dependence of the asparagine transport rate on its concentration can be described by the Michaelis-Menten equation with parameters: Km = 2.50 mM, V = 0.24 mmol/l cells per hour. Loading of erythrocytes with asparaginase does not influence their permeability to asparagine. Aspartate is accumulated inside these erythrocytes during incubation with asparagine, thus reflecting rapid transformation of penetrating asparagine by entrapped asparaginase.
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PMID:[Permeability of human erythrocytes to asparagine]. 407 79

Administration of either Escherichia coli asparaginase or guinea pig serum to C3H/HE mice with the 6C3HED lymphosarcoma is followed by depression of glycine in the tumor. This decrease in cellular glycine concentration does not occur in a tumor resistant to asparaginase. The inhibition of the lymphosarcoma by asparaginase can be reversed by intraperitoneal injection of asparagine or glycine. This reversal appears to be specific because lysine, threonine, serine, and aspartic acid were ineffective. Loss of cellular glycine may be more important than loss of asparagine because of the requirement for glycine in purine synthesis.
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PMID:Glycine inhibition of asparaginase. 490 4

Lymphoma 6C3HED-OG cells, known from previous work to be susceptible to the effects of guinea pig serum in vivo and dependent upon extrinsic asparagine for protein synthesis and growth in vitro, remained for the most part morphologically intact and countable in the electronic cell counter following exposures of 1 and 2 hr to the effects of heated (56 degrees C, 30 min) guinea pig serum injected into the peritoneal cavities of mice in which the lymphoma cells were growing rapidly; after exposures of 4 and 6 hr the bulk of the -OG cells remained still intact and countable in the cell counter, though by this time a small proportion of them (5 to 12%) proved stainable with eosin in wet preparations) hence were presumably nonviable. After 12, 16, and 24 hr of exposure, however, the bulk of the -OG cells were either lysed or fragmented, to the extent that they did not register in the cell counter. Morphologic studies of the cells exposed 16 and 24 hr to the effects of heated guinea pig serum in vivo, disclosed that most of the cells then remaining were either frankly necrotic or greatly altered otherwise, marked vacuolation of the cytoplasm being the most conspicuous alteration in cells not yet obviously necrotic. Long before the bulk of the Lymphoma 6C3HED-OG cells had become conspicuously changed morphologically following exposure to the effects of heated guinea pig serum in vivo, they manifested striking alterations in protein metabolism, as was disclosed by "pulse" studies with radioactive valine. For example, the protein metabolism of -OG cells, as measured by their incorporation of L-valine-C(14), was sharply curtailed following 15 min of exposure to heated guinea pig serum in vivo, as compared with valine incorporation by cells labeled immediately after exposure to the guinea pig serum. Following exposure to heated guinea pig serum during 60 min, -OG cells incorporated less than half as much L-valine-C(14) as did cells labeled immediately after exposure, and the incorporation of L-valine-C(14) was still less after 120 min of exposure. By contrast, Lymphoma -RG1 cells, known from previous work to be wholly insusceptible to the effects of guinea pig serum in vivo and independent of need for extrinsic asparagine for protein synthesis and growth in vitro, showed no curtailment whatever of protein synthesis following exposures to the effects of heated guinea pig serum in vivo during periods of 15, 60, and 120 min. Reasons are given for considering the prompt inhibition of protein synthesis in the asparagine-dependent -OG cells a direct result of asparagine-deprivation induced in vivo by the injected guinea pig serum, the L-asparaginase of which presumably converted the available L-asparagine of the host to L-aspartic acid that was not taken up by the -OG cells. The synthesis of deoxyribonucleic acid by Lymphoma 6C3HED-OG cells, as measured by the incorporation of thymidme-H(3), determined with the aid of liquid scintillation counting and autoradiography, was also altered by exposure of the lymphoma cells to the effects of heated guinea pig serum in vivo, though not during exposures of 15 and 60 min; only after an exposure of 120 min did the population of -OG cells incorporate notably less thymidine-H(3) than did control populations, though after 240 min of exposure the -OG cells incorporated less than one-fifth as much tritiated thymidineas had -OG cells exposed to heated guinea pig serum for 60 min or to heated horse serum for periods up to 240 min. Autoradiographs indicated that DNA synthesis by -OG cells normally proceeds at an intense level that leads to some 60% of these cells being heavily labeled in autoradiographs at any given time; after exposure to the effects of heated guinea pig serum during 2 and 4 hr in vivo, however, the lymphoma cells lost their ability to incorporate enough tritiated thymidine to become heavily labeled, but approximately the same proportion of them (56 to 58%) retained their ability to incorporate sufficient tritiated thymidine to become lightly labeled. The possibility is considered that the inhibition of DNA synthesis in the asparagine-dependent -OG cells exposed to the effects of heated guinea pig serum in vivo may be secondary to the previously manifest inhibition of protein synthesis. Further, in tests of ribonucleic acid metabolism of Lymphoma 6C3HED-OG cells after exposure to the effects of heated guinea pig serum in vivo during periods of 15, 60, 120, and 240 min, the findings indicated that the ability of the lymphoma cells to synthesize RNA, as measured by their capacity to incorporate uridine-5-H(3), remained unaltered during the exposures of 15, 60, and 120 min, but was substantially reduced following 240 min of exposure. The findings are considered in relation to the probability, disclosed in part by previous studies, that heated guinea pig serum brings about its effects upon Lymphoma 6C3HED-OG cells in vivo by providing active L-asparaginase in large amounts, which presumably converts the available (extracellular) asparagine of the host to aspartic acid, the latter not being taken up by the lymphoma cells in vivo or in vitro. Hence it seems likely that heated guinea pig serum in this way brings about a state of asparagine deprivation that is responsible for the sequential metabolic and morphologic alterations that become manifest in asparagine-dependent Lymphoma 6C3HED-OG cells following their exposure to the effects of guinea pig serum in vivo, as here described.
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PMID:Alterations in protein and nucleic acid metabolism of lymphoma 6C3HED-og cells in mice given guinea pig serum. 590 71

1. A procedure for partial purification of asparaginase from chicken liver is presented. 2. The bulk of the enzyme is located in the soluble fraction of chicken liver. 3. Molecular weights of chicken-liver asparaginase and of the guinea-pig serum enzyme, estimated by gel filtration, were 306000 and 210000 respectively. The Michaelis constants (K(m)) at 37 degrees and pH8.5 were 6.0x10(-5)m and 7.2x10(-5)m respectively. 4. At 50 degrees the chicken-liver enzyme was moderately stable, some activity being lost by aggregation; in dilute electrolyte solutions the activity rapidly diminished. 5. The anti-lymphoma effect of guinea-pig serum in mice carrying the 6C3HED tumour was confirmed. Chicken-liver asparaginase also showed an effect but in this case the enzyme preparation had to be administered repeatedly. 6. Guinea-pig serum asparaginase was stable for several days in mouse blood, after intraperitoneal injection, whereas chicken-liver asparaginase rapidly disappeared. 7. Aspartic acid beta-hydrazide was shown to be a competitive inhibitor of chicken-liver asparaginase with K(i) approx. 5.6x10(-4)m. In mice it produced an anti-lymphoma effect, as reported previously.
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PMID:Enzymes in cancer. Asparaginase from chicken liver. 603 63

Asparaginase-resistant subline L5178Y/Asp of murine lymphoblastic leukemia L5178Y cells was established from resistant clones isolated from soft agar cultures treated with Escherichia coli asparaginase. The L5178Y/Asp cells were found to be over 1000-fold more resistant to E. coli asparaginase, co-resistant to inhibitory effect of guinea pig serum (complement), more tumorigenic for syngeneic DBA/2 mice, and to grow much better (higher plating efficiency) in soft agar medium. With the use of the resistant subline in immunocytotoxicity-cytostasis test in the presence of guinea pig complement, we have been able to demonstrate the presence of tumor-associated antigen(s) on the L5178Y cells which is/are also demonstrable by enzyme-linked immunosorbent assay.
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PMID:Establishment of asparaginase- and guinea pig complement-resistant subline of murine lymphoblastic leukemia L5178y cells. 639 Feb 88

Kinetic parameters, substrate specificity and exclusivity of ligands at binding sites of L-glutaminase-L-asparaginase purified from Acinetobacter glutaminasificans were studied in order to gain knowledge about the dual activities of this enzyme and its inhibition by structural analogs. Both L-glutamine and L-asparagine, which showed similar Km (4 approximately 7 X 10(-5) M) and Vmax (molecular activity 1.0 min-1) values, were competitive with each other for the substrate binding site. The products, L-glutamic acid and L-aspartic acid, showed competitive inhibition with respect to either L-glutamine or L-asparagine as substrates. Multiple inhibition of the glutaminase activity by L-glutamic acid and L-aspartic acid indicated that these ligands are mutually exclusive at the product-releasing site. The initial rates of both of the enzyme's activities were competitively inhibited by the following inhibitors (in rates of both of the enzyme's activities were competitively inhibited by the following inhibitors (in decreasing order of activity): 6-diazo-5-oxo-L-norleucine (DON), L-methionine sulfoximine, azaserine, and Acivicin. DON and azaserine inhibited both the asparaginase and glutaminase activities in a time-dependent and irreversible manner. The kinetic data suggest an ordered mechanism with glutamine or asparagine as the first substrate and glutamic acid or aspartic acid, respectively, as the last product. These results also suggest that a single mechanism and a single set of binding sites are responsible for catalyzing both of the enzyme's activities. The data also showed that succinylated enzyme, which has a 10-fold increase of plasma half-life in animals and humans and, thus, has benefit as a cancer chemotherapeutic agent, retained its catalytic activity and maintained Km and Vmax values similar to the native enzyme.
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PMID:Kinetic properties and inhibition of Acinetobacter glutaminase-asparaginase. 683 61

The effect of L-aspartic acid, L-asparagine and/or L-asparaginase were compared with those of imipramine on immobility, number of defecations, increase of nociceptive threshold, and hypothermia, induced by forced swimming in rats. L-Aspartic acid was found to be as effective as imipramine in reducing the effects of forced swimming, presumable by normalizing the decreased level of endogenous L-aspartic acid, due to the inhibition of L-asparaginase activity and/or by stimulating the inhibited enzyme. The other treatments antagonized the immobility, but not the increased number of defecations. All compounds abolished the elevation of nociceptive threshold and hypothermia.
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PMID:Effects of L-aspartic acid, L-asparagine and/or L-asparaginase on forced swimming-induced immobility, analgesia, and decrease in rectal temperature in rats. 705 52


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