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)

Amino acid utilization was evaluated in seven children with acute lymphocytic leukemia treated with succinylated Acinetobacter glutaminase-asparaginase. All patients received food p.o. ad libitum and glucose-electrolyte solutions i.v.; four patients received an i.v. amino acid supplement (1.5 g/kg/day). Although all patients were in negative energy balance, there was a significant linear regression between nitrogen balance and nitrogen intake during Days 1 to 7 and Days 8 to 14 of the study. The slope of the regression line, reflecting exogenous nitrogen utilization, was not significantly different from that found in healthy young men ingesting adequate or subadequate energy intakes. The Y-intercept (-210 mg/kg/day) indicated an obligatory nitrogen loss that was much greater than normal. Most of the nitrogen loss was due to urinary excretion. Ammonia and urea accounted for 77 to 91% of the urine nitrogen. Urinary glutamate accounted for 4 to 10% of this loss. Urine protein excretion was abnormally high in each of the patients, ranging from 987 to 3440 mg/day. Urine excretion of N-acetyl-beta-glucosaminidase and beta 2-microglobulin was also abnormally high, despite normal blood urea nitrogen and serum creatinine, suggesting that these children had renal tubular dysfunction. The antileukemic effect of succinylated Acinetobacter glutaminase-asparaginase did not appear to be altered by amino acid supplementation. These data indicate that amino acid supplementation can improve nutritional status in patients treated with succinylated Acinetobacter glutaminase-asparaginase.
 ...
PMID:Amino acid utilization and urine protein excretion in children treated with succinylated Acinetobacter glutaminase-asparaginase. 701 7

The effects of Acinetobacter glutaminase-asparaginase (AGA) on protein and energy requirements were evaluated in mice bearing Ehrlich ascites tumors. In an initial experiment with normal mice, a zero protein diet resulted in a significant decrease in carcass nitrogen, liver nitrogen, and carcass energy relative to the animals on a normal, low, or high protein diet. In a second experiment, mice bearing Ehrlich ascites tumors were randomized into diet groups (zero or normal protein) and treatment groups (daily injections of AGA or 0.9% NaCl solution). In both treatment groups, the zero protein diet resulted in significant decreases in weight, liver nitrogen, carcass nitrogen, and carcass energy. Neither tumor nor AGA treatment affected body composition or the efficiency of nitrogen utilization. By Day 8, either the zero protein diet or AGA treatment significantly reduced ascites volume and tumor nitrogen content relative to controls. In a modification of Experiment 2, AGA treatment was stopped on Day 8, and all animals were given a normal protein diet. AGA, but not the zero protein diet, significantly enhanced ultimate survival. These experiments indicate that the requirements and utilization of energy and nitrogen are normal in mice with Ehrlich ascites tumor whether or not they are treated with AGA.
 ...
PMID:Nitrogen utilization in mice bearing Ehrlich ascites tumor treated with Acinetobacter glutaminase-asparaginase. 723 13

Cellular levels of an L-asparaginase in a Chlamydomonas species were found to be greater in nitrogen-limited batch cultures than in batch cultures grown in ample nitrogen. Cells grown in high nitrogen medium (5 mM NH4Cl) and suspended in nitrogen-free medium showed a 2- to 3.5-fold increase in activity after 24 to 48 h. This increase in activity was inhibited by cycloheximide and by the addition of high levels of combined nitrogen (5 mM NH4Cl, NaNO3, or L-asparagine), suggesting repression by ambient nitrogen levels as the mode of regulation of this enzyme. Derepressed L-asparaginase activity did not disappear in the presence of high concentrations of medium nitrogen, indicating the absence of an asparaginase-degrading system. Derepression of asparaginase by this organism was light dependent and inhibited by 3-(3',4'-dichlorophenyl)-1,1-dimethylurea suggesting a requirement for photosynthetic energy.
 ...
PMID:Regulation of L-asparaginase in a Chlamydomonas species in response to ambient concentrations of combined nitrogen. 724 99

L-asparaginase, a therapeutic agent for the treatment of acute lymphoblastic leukemia, was evaluated for its susceptibility to cold denaturation. It was found that the enzyme derived from Erwinia chrysanthemi loses its activity when exposed to freeze-thaw cycling. When it was frozen at -40 degrees C and thawed, the enzyme lost 67.3% of its activity; whereas, when frozen in liquid nitrogen (-190 degrees C), it lost almost all of its activity. Rheological studies of hetastarch showed that its viscosity dramatically increases with decreasing temperature, suggesting that at sub-zero temperatures it will create a highly viscous environment around the enzyme. It is proposed that this highly viscous environment retards the rate of conformational changes leading to losses in activity. Hetastarch solutions of various concentrations and degrees of hydroxyethylation were evaluated for their protective ability against the freeze-thaw denaturation of L-asparaginase. It was found that the cryoprotective effect of hetastarch with 0.8 degree of substitution at a concentration of 0.2% was sustained over many freeze-thaw cycles while that of the lesser substituted starch was not. The cryoprotective effect of hetastarch was compared to that of other commonly used additives such as glucose and lactose, which failed to protect the enzyme from freeze-thaw denaturation. In addition, the protective effect of a monomer of hetastarch was evaluated in order to distinguish whether the protective effect of hetastarch was due to physicochemical interactions with the individual monomer units or to its polymeric nature. The monomer showed significant cryoprotection through the first freeze-thaw cycle which was not sustained over additional freeze-thaw cycles.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:The effect of hetastarch on the stability of L-asparaginase during freeze-thaw cycling. 754 44

Upon the establishment of an effective nitrogen-fixing symbiosis in amide-transporting plants the enzymatic activity and transcript levels of L-asparaginase are dramatically decreased. This decrease in L-asparaginase activity is essential for the correct functioning of the Rhizobium-legume symbiosis in lupin in which asparagine, synthesized from recently fixed nitrogen, is exported to aerial parts of the plant for use in growth and development. Concomitant with this decrease in L-asparaginase transcript a DNA-binding protein was detected in the nodules. This binding protein was not detectable in ineffective nodules, in nodules treated with nitrate, or in root tips, mature roots, developing flowers or developing seeds. The DNA-binding activity was shown to interact with a 59 bp sequence proximal to the transcription start site. Within this sequence a CTAAAAT direct repeat and a ACTGT/TGTCA incomplete inverted repeat were implicated in the binding of protein to the DNA by DNase I protection experiments. Competitive binding studies with synthesized binding sites were consistent with the CTAAAAT/TGTCA sequence pair proximal to the transcription start site having the highest affinity for the DNA-binding protein. We postulate that this DNA-binding protein is associated with repression of L-asparaginase gene expression in mature lupin root nodules.
 ...
PMID:Repression of the L-asparaginase gene during nodule development in Lupinus angustifolius. 794 78

Saccharomyces cerevisiae produces two L-asparaginases (ASPs), intracellular ASP I and cell-wall ASP II. In this report, the ASP-I-encoding gene, ASP1, has been identified by homology cloning based on the structures of ASPs from other organisms. Its deduced protein product has a subunit M(r) of 41,414, and shows substantial sequence homology to the bacterial amidohydrolase family. The product of the S. cerevisiae ASP3 gene, a further member of this family, encoding the nitrogen catabolite-regulated cell-wall ASP II, has 46% overall sequence identity to ASP1. Duplication of ancestral asparaginase genes, resulting in separate intra- and extracellular isozymes, appears to have occurred independently in the prokaryotic and eukaryotic lineages. Exact physical mapping of the new cloned ASP1 gene locates it 73% of the distance from the left telomere of chromosome IV, at a position precisely matching the known genetic map location of ASP1. This, along with the structural features of the clone, confirms that ASP1 is the structural gene encoding cytoplasmic ASP I in S. cerevisiae. Sequence analysis of the ethylmethanesulfonate-induced asp1-12 allele of strain XE101-1A revealed a C-->T transition altering Ala176 to Val. This residue lies within a highly conserved region, and the results suggests a critical function for Ala176 in ASP function. Expression of ASP1 and other recombinant ASPs may allow access to improved products for use in the chemotherapy of leukaemia.
 ...
PMID:The ASP1 gene of Saccharomyces cerevisiae, encoding the intracellular isozyme of L-asparaginase. 802 56

The emetic effects of five anticancer drugs, cyclophosphamide, nitrogen mustard-N-oxide, actinomycin D, 5-fluorouracil and L-asparaginase, and the effects of bilateral abdominal vagotomy and bilateral greater splanchnic nerve section or a 5-HT3 receptor antagonist on the emesis induced by these drugs were investigated in dogs. Cyclophosphamide (20 mg/kg, i.v.), nitrogen mustard-N-oxide (5 mg/kg, i.v.) and actinomycin D (50 micrograms/kg, i.v.) caused vomiting in dogs with a long latency period. 5-Fluorouracil (5 mg/kg, i.v.) and L-asparaginase (2000 K.U./kg, i.v.) failed to induce vomiting. Bilateral abdominal vagotomy and bilateral greater splanchnic nerve section completely inhibited the vomiting induced by the former three anticancer drugs. Furthermore, the vomiting was inhibited completely by intravenous administration of ICS205930 (2 x 0.1 mg/kg), a 5-HT3 receptor antagonist. These results suggest that activation of visceral afferents through 5-HT3 receptors mediates the vomiting induced by cyclophosphamide, nitrogen mustard-N-oxide and actinomycin D.
 ...
PMID:Emetic effects of anticancer drugs and involvement of visceral afferent fibers and 5-HT3 receptors in dogs. 811 85

From 1975 to 1989, 71 acute lymphoblastic leukemia patients aged 15 to 81 years (median 46 years) were treated at Jichi Medical School. Fifty-eight patients (81.7%) achieved complete remission (CR). Median CR duration was 219 days, and the probability of being in continuous CR at 3 years was 8.9%. Median survival was 462 days, and the probabilities of being alive at 3 and 5 years were 19.8% and 7.3%, respectively. The new regimen introduced from 1987 consisted of remission induction with L-asparaginase, daunomycin, vincristine and prednisolone, followed by intensive consolidation and maintenance. However, the treatment failed to improve outcome. The factor unfavorable for achieving early CR after first-line treatment regimen was the presence of myeloid antigen, and that for achieving final CR after second-line treatment regimen was advanced age. The factors unfavorable for remission duration were high leukocyte count and late CR. Those unfavorable for survival were advanced age and elevated blood urea nitrogen. Further improvement in the design of new protocols which include the use of several cytokines and autologous bone marrow transplantation may result in prolonged disease-free survival.
 ...
PMID:[Treatment of 71 adult acute lymphoblastic leukemia]. 837 76

Rhizobium etli mutants unable to grow on asparagine as the nitrogen and carbon source were isolated. Two kinds of mutants were obtained: AHZ1, with very low levels of aspartase activity, and AHZ7, with low levels of asparaginase and very low levels of aspartase compared to the wild-type strain. R. etli had two asparaginases differentiated by their thermostabilities, electrophoretic mobilities, and modes of regulation. The AHZ mutants nodulated as did the wild-type strain and had nitrogenase levels similar to that of the wild-type strain.
 ...
PMID:Isolation and characterization of Rhizobium etli mutants altered in degradation of asparagine. 906 57

A gram-negative, rod-shaped bacterium capable of utilizing L-asparagine as its sole source of carbon and nitrogen was isolated from soil and identified as Enterobacter cloacae. An intracellularly expressed L-asparaginase was detected and it deaminated L-asparagine to aspartic acid and ammonia. High-pressure liquid chromatography analysis of a cell-free asparaginase reaction mixture indicated that 2.8 mM L-asparagine was hydrolyzed to 2.2 and 2.8 mM aspartic acid and ammonia, respectively, within 20 min of incubation. High asparaginase activity was found in cells cultured on L-fructose, D-galactose, saccharose, or maltose, and in cells cultured on L-asparagine as the sole nitrogen source. The pH and temperature optimum of L-asparaginase was 8.5 and 37-42 degrees C, respectively. The half-life of the enzyme at 30 degrees C and 37 degrees C was 10 and 8 h, respectively.
 ...
PMID:Isolation and characterization of Enterobacter cloacae capable of metabolizing asparagine. 986 75


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>