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 radiometric technique for measuring l-asparagine in small samples of biological origin is presented. After removal of l-glutamate and l-aspartate by enzymic decarboxylation, l-asparagine in the sample is hydrolysed to l-aspartate with l-asparaginase from Escherichia coli. The l-aspartate so generated is then enzymically transaminated with 2-oxo[1-(14)C]glutarate yielding l-[1-(14)C]glutamate. After specific chemical removal of unchanged 2-oxo[1-(14)C]glutarate, the l-[1-(14)C]glutamate generated is determined by scintillation counting of the radioactivity. This technique can measure the concentration of l-asparagine present in approx. 1mul of mouse blood, and is capable of detecting as little as 25pmol of the amide. Illustrative applications of the method are presented and discussed, including measurement of the l-asparagine content of the mouse hypophysis.
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PMID:A radiometric technique for measuring L-asparagine in picomole quantities. 465 28

The biosynthesis of asparaginase II in Saccharomyces cerevisiae is subject to nitrogen catabolite repression. In the present study we examined the physiological effects of glutamate auxotrophy on cellular metabolism and on the nitrogen catabolite repression of asparaginase II. Glutamate auxotrophic cells, incubated without a glutamate supplement, had a diminished internal pool of alpha-ketoglutarate and a concomitant inability to equilibrate ammonium ion with alpha-amino nitrogen. In the glutamate auxotroph, asparaginase II biosynthesis exhibited a decreased sensitivity to nitrogen catabolite repression by ammonium ion but normal sensitivity to nitrogen catabolite repression by all amino acids tested.
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PMID:Nitrogen catabolite repression in a glutamate auxotroph of Saccharomyces cerevisiae. 612

A man with a chronic schizophrenia-like psychotic disorder had fasting plasma asparagine concentrations that were consistently 4 to 8 SD above the normal level. Asparagine levels were also high in his cerebrospinal fluid (CSF) and erythrocytes. Ornithine, proline, and glutamate concentrations were irregularly high in fasting plasma, and gamma-aminobutyric acid (GABA) concentrations were elevated in CSF. Whether or not these biochemical abnormalities were related to the psychotic disorder is unclear. However, increased asparagine concentrations, possibly due to an enzymatic deficiency of asparaginase, could lead to deregulation of polyamine biosynthesis and to excessive production of GABA from putrescine. These biochemical changes could in turn cause disordered brain function. A search in mentally ill patients for metabolic abnormalities involving asparagine, or other amino acids, might hasten elucidation of the biochemical basis of the schizophrenias.
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PMID:Hyperasparaginemia in a schizophrenic patient. 683 Sep 27

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.
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PMID:Amino acid utilization and urine protein excretion in children treated with succinylated Acinetobacter glutaminase-asparaginase. 701 7

Succinylated Acinetobacter glutaminase-asparaginase (SAGA) has broader antitumor activity than Escherichia coli L-asparaginase in experimental systems; moreover, drug resistance does not develop in tumor cell lines initially sensitive to this enzyme. We have investigated the pharmacology and toxicology of SAGA after both single-dose and serial daily dose injections in 20 adult patients. Glutaminase activity in plasma after i.v. injection of single doses did not follow simple first-order kinetics (half-life during the initial 24 hr was 21 +/- 9 hr. A linear relation was observed between increasing doses of SAGA and resultant levels of plasma enzyme activity and blood glutamate. Assay of whole blood which had been deproteinized immediately following phlebotomy showed that single doses of SAGA lowered glutamine only transiently to nondetectable levels; serial daily doses were required to achieve and maintain continuous glutamine depletion. Reversible depression of the central nervous system, ranging from encephalopathy to coma, occurred in a dose-related manner and was dose limiting. Other prominent reactions included respiratory alkalosis, hyperglycemia, nausea, and vomiting. Transient antitumor effects were noted in two patients with solid tumors and in two patients with leukemia. SAGA causes considerable neurotoxicity in adults which requires close patient monitoring. Phase II studies in leukemic patients are in progress.
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PMID:Phase I evaluation of succinylated Acinetobacter glutaminase-asparaginase in adults. 743 89

The treatment of NIH3T3 cells with L-asparaginase causes a complete and reversible growth arrest with a decrease of cell number in the first 2 days. The enzyme induces impressive morphological changes that have been studied exploiting eosin in fixed cells and calcein in intact cells as sources of fluorescence for confocal microscopy. The first changes are observed after 12 h of treatment and the process is complete after 48 h. Both nucleus and cytoplasm shrink, while cells round and lose processes. Eventually most cells break; several debris include strongly hematoxylinic bodies negative for eosin fluorescence. Some cells neither round nor break in fragments. Throughout the process cells and fragments retain calcein fluorescence, thus indicating the integrity of the cell membrane. A rapid depletion of the intracellular pools of both glutamine and glutamate occurs in treated cells, followed by a decrease in DNA and protein syntheses, while the cell content of ATP, the transmembrane gradient of sodium, and the active transport of amino acids are scarcely affected. It is concluded that (i) L-asparaginase induces an apoptotic process in NIH3T3 cells that is forerun by a marked intracellular depletion of glutamate and glutamine; and (ii) although the enzyme completely suppresses cell proliferation, only a subset of cells undergoes apoptosis upon treatment. These findings provide a model for the characterization of factors that determine cell sensitivity to the effects of L-asparaginase.
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PMID:Characterization of apoptotic phenomena induced by treatment with L-asparaginase in NIH3T3 cells. 755 35

When the expression of a Ha-ras oncogene is triggered in NIH3T3 cells, a progressive inhibition of sodium dependent transport of anionic amino acids through system X-AG is observed. After 48 h of ras expression the transport activity of system X-AG is almost abolished, while other transport systems involved in anionic amino acid transport are unaffected or even stimulated. In the presence of high extracellular concentrations of glutamine, the intracellular concentration of glutamate is comparable in ras expressing and non-expressing cells. On the contrary, when the extracellular pool of glutamine is depleted by the enzyme L-asparaginase, intracellular glutamate decreases at a much faster rate in ras expressing, low-transport cells. These results suggest that transport system X-AG significantly contributes to the homeostasis of intracellular glutamate under conditions of glutamine deprivation.
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PMID:Suppression of anionic amino acid transport impairs the maintenance of intracellular glutamate in Ha-ras-expressing cells. 759 18

The review summarizes and analyzes experimental evidence for the properties of glutamine(asparagine)ase from Pseudomonas aurantiaca-548. The enzyme is a tetramer having a molecular weight of 148 kD and consisting of 4 identical subunits having a molecular weight of 37 kD. For glutaminase activity, the optimum pH is in the range of 6.0-8.0, asparaginase activity increases as pH rises. The enzyme is maximally stable at pH 6.8-8.0. The Michaelis constants are 5.3 +/- 0.7 x 10(-6) M for L-glutamine and 5.7 +/- 0.1 x 10(-6) M for asparagine. The reaction products L-aspartate and L-glutamate are competitive inhibitors anazaserine and 6-diase-5-oxo-1-norleucine are classic inhibitors of glutamine(asparagine)ase. The review also presents data on the conditions for culturing Ps. aurantiaca, on the procedures for isolating glutamine(asparagine)ase from biomass of this microbe, on substrate specificity. The results of searching for regulators of catalytic activity, as well as agents enhancing the resistance of enzymes to heat exposures are considered in the paper. Whether the properties of glutamine(asparagine)ase are in conformity with the criteria for primary choice of promising antitumor agents is discussed.
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PMID:[Molecular and catalytic properties of bacterial glutamin-(asparagin-)ase]. 775 33

Helicobacter pylori can utilise amino acids as the sole carbon energy source. The present study demonstrated that H. pylori grown in continuous culture in a defined medium containing glucose and amino acids utilised alanine, arginine, asparagine, aspartate, glutamine, glutamate, proline and serine. Specific asparaginase and glutaminase enzymes deaminated asparagine and glutamine respectively to aspartate and glutamate, with the production of ammonia. The glutaminase activity was inhibited by 6-diazo-5-oxo-L-norleucine. All the 13 strains of H. pylori tested produced both glutaminase and asparaginase activities. Glutamine is important in the health of the gastric and intestinal mucosa and is a primary energy source for lymphocytes. Depletion of glutamine at the site of H. pylori infection may be of significance in the pathogenesis of H. pylori-associated diseases such as peptic ulcer and gastric cancer.
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PMID:Amino acid utilisation and deamination of glutamine and asparagine by Helicobacter pylori. 929 92

We present the setup of a flow injection analysis system designed for on-line monitoring of glutamate and glutamine. These amino acids represent a major energy source in mammalian cell culture. A cycling assay consisting of glutamate dehydrogenase and aspartate aminotransferase produces NADH proportional to the glutamate concentration in the sample. NADH is then measured spectrophotometrically. Glutamine is determined by conversion to glutamate which is fed into the cycling assay. The conversion of glutamine to glutamate is catalyzed by asparaginase. Asparaginase was used in place of glutaminase due to its relatively high reactivity with glutamine and a pH optimum similar to that of glutamate dehydrogenase. The enzymes were immobilized covalently to activated controlled pore glass beads and integrated into the flow injection analysis system. The application of the immobilized enzymes and the technical setup are presented in this paper.
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PMID:Enzyme-based flow injection analysis system for glutamine and glutamate in mammalian cell culture media. 1003 69


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