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)

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

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

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

Of 55 males, currently above 18 years of age, diagnosed with and treated for different malignancies in childhood between 1960 and 1985 at a single institution, 28 (51%) were azoospermic. The age of the patient, testicular irradiation, four different therapeutic agents (L-asparaginase, cyclophosphamide, doxorubicin, vincristine) and one combination (MOPP, nitrogen mustard, vincristine, procarbazine, prednisone) were each associated with the risk of azoospermia. However, in multivariate analysis vincristine had the statistically most significant independent effect on the risk of azoospermia, the risk being 5-fold (95% confidence limits 1.3-18.8, P = 0.02) that in patients who had not received vincristine. The risk of azoospermia in patients who had received cyclophosphamide was 3.4-fold (0.95-12.3, P = 0.06) and in those who had received testicular irradiation it was 8.2-fold (0.75-90.9, P = 0.09) that of others. Normospermia (22% of patients) was not incompatible with any of the more commonly used modes of therapy. We conclude that vincristine may have a previously unrecognised important role in causing azoospermia, possibly irreversible, when administered in childhood or adolescence.
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PMID:Vincristine is associated with the risk of azoospermia in adult male survivors of childhood malignancies. 132 21

We studied the histamine-releasing activity of several antineoplastic drugs on rat pleural and peritoneal mast cells. The drugs tested included the nitrogen mustards cyclophosphamide and ifosfamide, the nitrosourea carmustine, the triazene dacarbazine, the folic acid analogue methotrexate, the pyrimidine analogue cytarabine and fluorouracil, the vinca alkaloids vinblastine, vincristine and Vinorelbine, the epipodophyllotoxins etoposide and teniposide, and the enzyme L-asparaginase. Methotrexate, carmustine, fluorouracil, vinblastine and vincristine failed to elicit histamine release on rat mast cells. All of the other drugs evoked histamine release in both the presence and the absence of extracellular calcium, but ifosfamide, cytarabine and asparaginase induced a much lower release in the absence of this cation. The response elicited by cytarabine and etoposide was much higher in pleural than in peritoneal mast cells. These results indicate that some antineoplastic drugs may directly activate the release of histamine, which could contribute to some of their secondary effects.
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PMID:Non-immunological release of histamine from rat mast cells elicited by antineoplastic agents. 137 74

The levels of urease and asparaginase were elevated 25- and 20-fold, respectively, in extracts of Bacillus subtilis cells grown in medium containing nitrogen sources that are poor sources of ammonium (NH4+) compared with the levels seen in extracts of cells grown in medium containing nitrogen sources that are good sources of NH4+. To determine whether a collection of genes whose expression responds to nitrogen availability could be isolated, a library of Tn917-lacZ insertions was screened for nitrogen-regulated beta-galactosidase expression. Two fusion strains were identified. beta-Galactosidase expression was 26- and 4,000-fold higher, respectively, in the nrg-21::Tn917-lacZ and the nrg-29::Tn917-lacZ insertion strains during NH4(+)-restricted growth than during growth on nitrogen sources that are good sources of NH4+. PBS1 transduction analysis showed that the nrg-21::Tn917-lacZ insertion mapped between gutB and purB and that the nrg-29::Tn917-lacZ insertion mapped between degSU and spoIID. The repression of expression of these four gene products during growth on good sources of NH4+ required the wild-type glutamine synthetase protein but not the glutamine synthetase regulatory protein, GlnR.
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PMID:Identification of genes and gene products whose expression is activated during nitrogen-limited growth in Bacillus subtilis. 167 Sep 35

A positive, genetic selection against the activity of the nitrogen regulatory (NTR) system was used to isolate insertion mutations affecting nitrogen regulation in Klebsiella aerogenes. Two classes of mutation were obtained: those affecting the NTR system itself and leading to the loss of almost all nitrogen regulation, and those affecting the nac locus and leading to a loss of nitrogen regulation of a family of nitrogen-regulated enzymes. The set of these nac-dependent enzymes included histidase, glutamate dehydrogenase, glutamate synthase, proline oxidase, and urease. The enzymes shown to be nac independent included glutamine synthetase, asparaginase, tryptophan permease, nitrate reductase, the product of the nifLA operon, and perhaps nitrite reductase. The expression of the nac gene was itself highly nitrogen regulated, and this regulation was mediated by the NTR system. The loss of nitrogen regulation was found in each of the four insertion mutants studied, showing that loss of nitrogen regulation resulted from the absence of nac function rather than from an altered form of the nac gene product. Thus we propose two classes of nitrogen-regulated operons: in class I, the NTR system directly activates expression of the operon; in class II, the NTR system activates nac expression and the product(s) of the nac locus activates expression of the operon.
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PMID:Role of the nac gene product in the nitrogen regulation of some NTR-regulated operons of Klebsiella aerogenes. 197 23

Purified preparations of asparaginase II of Saccharomyces cerevisiae exhibit two protein bands upon sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Cloning and sequencing of the ASP3 gene, and partial amino acid sequencing as asparaginase II, imply that both bands are encoded by ASP3 but have different N termini. Northern blot analysis using the cloned ASP3 gene as a probe indicates that nitrogen catabolite repression of asparaginase II is achieved by alteration in mRNA levels. Deletion of sequences greater than 600 base pairs upstream from the initiation AUG codon results in an altered response to certain nitrogen sources in strains containing the truncated gene.
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PMID:Asparaginase II of Saccharomyces cerevisiae. Characterization of the ASP3 gene. 304 86

Of five amidohydrolase activities subject to nitrogen metabolite repression in Aspergillus nidulans, L-asparaginase shows clearest evidence of also being subject to repression by atmospheric oxygen. Such oxygen repressibility is only evident under nitrogen metabolite derepressed conditions. Asparaginase levels are also considerably elevated by areA300, an altered function allele of the positive acting wide domain regulatory gene areA mediating nitrogen metabolite repression and are drastically reduced by loss of function mutations in areA. A. nidulans has two L-asparaginase enzymes and it has been shown by the use of appropriate mutants that these regulatory effects are exerted on the expression of that specified by the ahrA gene but probably not that specified by the apnA gene.
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PMID:An asparaginase of Aspergillus nidulans is subject to oxygen repression in addition to nitrogen metabolite repression. 304 73


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