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)

A systematic search has been made for inhibitors of L-asparagine synthetase (L-glutamine hydrolyzing, EC 6.3.5.4) from leukemia 5178Y/AR, a rodent neoplasm resistant to the oncolytic enzyme L-asparaginase (EC 3.5.1.1), The classes of chemicals examined in this search included substrate and product analogs, agents capable of reacting with sulfhydryl functions, and a variety of modifiers whose mechanism of interaction with proteins is known. In general, antagonists of L-glutamine and thiol reagents proved to be the most effective inhibitors of L-asparagine synthetase from this tumor source. Within these groups, certain structural prerequisites to inhibition are reported. Attempts to correlate oncolytic potency with enzyme-inhibitory potency were unsuccesful.
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PMID:Inhibitors of L-asparagine synthetase, in vitro. 1 84

The nutritional requirements and culture conditions affecting biosynthesis of L-asparaginase in a mutant of Escherichia coli HAP designated strain A-1 were studied. Asparaginase activity was increased by the addition of L-glutamic acid, L-glutamine, or commercial-grade monosodium glutamate. The rate of enzyme synthesis was dependent on the interaction between the pH of the culture and the amount of oxygen dissolved in the medium. A critical oxygen transfer rate essential for asparaginase formation was identified, and a fermentation procedure is described in which enzyme synthesis is controlled by aeration rate. Enhancement of L-asparaginase activity by monosodium glutamate was inhibited by the presence of glucose, culture pH, chloramphenicol, and oxygen dissolved in the fermentation medium.
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PMID:Effect of culture conditions on synthesis of L-asparaginase by Escherichia coli A-1. 1 9

The concentration dependence of the rate of hydrolysis of L-asparagine by Escherichia coli L-asparaginase (L-asparagine amidohydrolase, EC 3.5.1.1) has been measured over the range pH 4.5 to pH 9.1 by a direct spectrophotometric assay at 220 nm and by a coupled assay utilizing glutamate dehydrogenase to detect the ammonia produced. The velocity of the hydrolysis reaction at saturating levels of substrate is independent of pH over this interval. The plot of V/km over the same interval is bell-shaped, being dependent on pKa values of 6.58 and 8.69. The higher pKa is attributed to the amino group of asparagine. The lower pKa is associated with the enzyme active site and is probably due to an imidazole group.
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PMID:pH dependence of the kinetic parameters of L-asparaginase. 2 62

A mating between Escherichia coli 4318 (thi leu Las- Hfr) and E. coli A-1 (Met- Las+ F-) resulted in the formation of prototrophic recombinants having L-asparaginase activities at three distinct levels. The physiology of L-asparaginase synthesis in these recombinants is decribed. One class of recombinants produced significantly more L-asparaginase than E. coli A-1. L-Asparaginase synthesis in the recombinants was inhibited by the presence of dissolved oxygen in the medium and was transiently repressed by the presence of glucose in the same manner as that observed in the parental strains. L-Asparaginase activity was increased by the addition of oxalacetate as well as other members of the tricarboxylic acid cycle.
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PMID:Physiology of L-asparaginase synthesis in recombinants of Escherichia coli A-1. 2 25

First, lymphocyte transplantation into total body-irradiated rats is discussed. The effect on spleen colony formation caused by the transplantation of untreated lymphocytes, as well as of lymphocytes previously incubated with PHA, or with PHA plus L-asparaginase, or with lymphokines, was studied. Then the effect of the urinary colony-stimulating factor in vitro, and the in vitro feeder-layer activity of leucocytes on colony formation of human and mice bone marrow cells in haematological diseases is dealth with. The injection of rat lymphocytes previously incubated for 24 hours with PHA resulted in a higher number and a larger size of colonies in the spleen of the recipient rats. Lymphocytes preincubated with lymphokines gave rise to the formation of spleen colonies which were larger than those developing after the injection of untreated lymphocytes. When the lymphocytes were previously incubated with PHA plus L-asparaginase, PHA failed to stimulate colony formation in the spleen. The phenomenon is explained by assuming that PHA, as an aspecific stimulator of cell division, initiated the division of CFUs, thus the CFUs content of the preincubated samples increased, resulting in an increase in the number of colonies formed after the transplantation of lymphocytes pretreated with PHA. Another possible explanation is that CFUs division, or their spleen take is enhanced by the immunocompetent lymphocytes activated by PHA, either directly or via soluble mediators produced or released by immunocompetent lymphocytes such as lymphokines. The study of colony-forming cells and colony-stimulating activity in primary myelofibrosis (PM) showed an increase in the number of circulating CFUc in this condition, and an abnormal density of these cells reaching a peak below 1.062. The lowering of CSA in the first two peripheral blood gradient fractions agrees with the observation in the same fractions of a high percentage of CFUc at the expense of the CSC population. Thus, double cell population seems to exist in PM. One is greatly abnormal with a low specific density and high plating efficiency, whereas the other population is almost normal, showing a higher specific density and a lower plating efficiency.
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PMID:Experimental and clinical investigations on stem cell take and colony formation. 2 25

1. The mouse Gardner lymphoma 6C3HED was grown in ascites fluid in a form sensitive to the action of L-asparaginase (line 1), in another form which was resistant to L-asparaginase (line 2) and in a third form with partial sensitivity to L-asparaginase (line 3). 2. The L-asparaginyl-tRNA synthetase activities of extracts of the tumour cells, cultured both in the mouse and in vitro, were determined. Two of the lines, 1 and 3, in early passage numbers, showed a derepression mechanism involving L-asparagine. Mutation occurred with these lines resulting in the L-asparaginyl-tRNA synthetase activity of all the tumour cell lines being the same. 3. Cells of line 1 had low L-asparagine synthetase activity, which was unchanged by altering the supply of L-asparagine in vitro. Cells of lines 2 and 3 exhibited L-asparagine synthetase activities, which changed with the supply of L-asparagine. 4. It is not certain that L-asparagine synthetase activity of L-asparaginase-sensitive cells is controlled by L-asparaginyl-tRNA acting as a corepressor.
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PMID:L-asparaginyl-tRNA synthetase and L-asparagine synthetase activities of L-asparaginase-sensitive and -resistant forms of the mouse Gardner lymphoma 6C3HED. 3 36

A Chlamydomonas species isolated from a marine environment possesses an L-asparaginase, an enzyme not yet reported in the microalgae. This enzyme enabled the organism to grow as well with asparagine as sole nitrogen source as with inorganic nitrogen sources (NO3-, NH4+). Only the amide nitrogen was used for growth since growth did not occur on aspartate and aspartate accumulated in the media when cells were either grown on asparagine or during short-term incubations with L-[U-14C]asparagine. Cells grown on NO3-, NH4+, or L-asparagine in batch culture possessed equivalent asparaginase activities. However, nitrogen-limited cells possessed four times the activity of cells grown with sufficient nitrogen for normal growth, regardless of the possessed the lowest activity per cell, while lag phase and stationary phase cells possessed greater activity. The enzyme behaved like a periplasmic space enzyme since (1) breaking the cells did not release into solution more activity than was shown by whole cells and (2) whole cells converted L-[U-14C]asparagine to [14C]aspartate with little intracellular accumulation of radioactivity. Cell-free preparations of the enzyme possessed a Km value for asparagine of 1.1 x 10-4 M, with no glutaminase activity.
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PMID:Asparagine metabolism and asparaginase activity in a euryhaline Chlamydomonas species. 4 71

Production of L-asparaginase by two soil isolates, identified as S. karnatakensis and S. venezuelae, was investigated under different environmental and nutritional conditions. The presence of carbon sources, other than starch, in the growth medium or amino acids, other than L-asparagine-inhibited the enzyme biosynthesis. L-aspartic inhibited growth and enzyme production, due to a feedback mechanism, and/or lowering the pH value. Both organisms were stimulated to produce more enzyme with increasing concentrations of starch and L-asparagine, however, the optimum starch and L-asparagine concentration depended on the tolerance of the organism to low and high pH, respectively. Aeration stimulated growth, but not enzyme production, and both organisms produced more enzyme in static cultures than in shaken cultures.
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PMID:Production of L-asparaginase by Streptomyces karnatakensis and Streptomyces venezuelae. 4 13

Five actinomycete isolates (all belonged to the genus Streptomyces), capable of producing detectable amounts of L-asparaginase, were isolated from the soil of Kuwait after enrichment. The three most potent enzyme producers were identified as different strains of Streptomyces collinus. Factors affecting enzyme production by the strongest strain were examined. Synthetic media with asparagine as a nitrogen source stimulated more enzyme production than natural media. Starch and asparagine at final concentrations of 1 and 0.8%, respectively, were optimum for enzyme production. An initial pH of 8.5 for the growth medium and an incubation temperature of 28-30 degrees C in a static culture for 6 days stimulated enzyme production by the examined strain of Streptomyces collinus.
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PMID:L-asparaginase-producing Streptomyces from the soil of Kuwait. 4 99

Eight isolates capable of producing varying quantities of L-asparaginase and all identified as members of the genus Streptomyces were isolated from the soil and a suitable technique for the assay of intracellular L-asparaginase in actinomycetes was developed. The most potent L-asparaginase producer was identified as a strain of Streptomyces karnatakensis. Static cultures of S. karnatakensis showed maximum enzyme activity with almost maximum growth while shaken cultures exhibited their activity after 48 hours of growth. This phenomenon is discussed in terms of possible feedback mechanism and/or the biosynthesis of certain pigments. L-asparaginase of S. karnatakensis proved to be mostly intracellular and the presence of L-asparagine in the culture medium though, stimulating yet not essential for the enyzme biosynthesis. Cells grown on L-asparagine showed amidase activity with other amides but at a reduced rate.
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PMID:Activity of L-asparaginase in cells of Streptomyces karnatakensis. 4


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