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)

Desialised orosomucoid (alpha-1-acidic glycoprotein) was coupled to Pseudomonas 7A glutaminase-asparaginase by glutaraldehyde, iodinated and injected into mice. The half-life of radioactivity and glutaminase activity in plasma was about 7 min. Radioactivity and glutaminase activity in the liver reached a peak at about 20 min. The radioactivity in liver then declined with a half-life of about 20 min. Enzyme activity in liver declined with a half-life of about 10 min. The ratio of enzyme activity to radioactivity was lower in the liver than in plasma at all times during the experiment, indicating rapid hepatic inactivation of the enzyme. Uptake into the liver could be blocked by excess desialised orosomucoid. Glutamine levels in the liver were about 10% of normal for 44 min but returned to 50% of normal by 93 min. Intestines, kidney and spleen failed to exhibit any appreciable uptake of desialated orosomucoid glutaminase-asparaginase.
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PMID:Kinetics of uptake and activity in mouse liver of glutaminase coupled to desialated orosomucoid. 62 51

Acinetobacter glutaminase-asparaginase (AGA) and Escherichia coli asparaginase were compared for their effects on plasma and tissue levels of amino acids, ammonia, and glutamyl transferase activity in the mouse. Free asparagine was depleted similarly in plasma and tissues by both enzymes. AGA treatment produced partial depletion of glutamine concentrations in muscle, spleen, small intestine, and liver. Brain and kidney glutamine concentrations actually rose with treatment. Despite over 100-fold increase in plasma glutamate, only the kidney showed a substantial increase in free glutamate levels during AGA treatment. Glutamine biosynthesis measured by glutamyl transferase activity showed an appreciable increase only in the kidney. Ammonia levels in tissues and plasma rose 1.3- to 4.3-fold. In general, E. coli asparaginase treatment had much less effect on these measurements than did AGA. The changes in these levels are discussed in relation to sites of possible toxicity and antitumor effects.
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PMID:Effect of Acinetobacter glutaminase-asparaginase treatment on free amino acids in mouse tissues. 109 50

L-Asparaginase has long been used in the treatment of acute lymphoblastic leukemia or malignant lymphoma in childhood. To determine cell type specific sensitivity to this drug, the L-asparaginase-mediated inhibition of blastogenesis of human peripheral T or B lymphocytes was compared. The rate of incorporation of [3H]-thymidine into the DNA of either T lymphocytes due to phytohemagglutinin (PHA) or B lymphocytes due to Staphylococcus aureus Cowan I (SAC) was measured by the addition of Escherichia coli L-asparaginase in the medium. The blastogenic response of either T or B lymphocytes was also determined in medium depleted of exogenous asparagine and/or glutamine, both of which are hydrolyzed by this enzyme. The in vitro blastogenesis of either human T lymphocytes due to PHA or B lymphocytes due to SAC was inhibited by the inclusion of asparaginase in the medium. The deprivation of exogenous asparagine did not have any inhibitory effect on the blastogenic response of both T and B lymphocytes to each mitogen. On the other hand, the glutamine concentration in the culture medium provided a critical influence on the proliferative response of T and B lymphocytes. The rate of incorporation of [3H]-thymidine into DNA was increased markedly as the concentration of glutamine was increased from 2(-7)-2 mmol/l. It is concluded that the mechanism of inhibition of PHA- or SAC-stimulated lymphocyte blastogenesis by L-asparaginase is not asparagine deprivation but glutamine deprivation. Glutamine, which is the most abundant amino acid, is thought to have an important role in the immune response of lymphocytes.
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PMID:The inhibition of lymphocyte blastogenesis by asparaginase: critical role of glutamine in both T and B lymphocyte transformation. 128 1

Glutamine depletion strongly inhibits the replication of Rauscher murine leukaemia retrovirus (RLV) in vitro. Pseudomonas 7A glutaminase-asparaginase (PGA), capable of depleting glutamine and asparagine for prolonged periods, was used to determine the therapeutic effectiveness of glutamine depletion in mice infected with RLV or Friend virus. During PGA treatment of viraemic animals, serum reverse transcriptase activity fell to control levels and infected animals did not develop splenomegaly. The therapeutic results obtained with PGA compared favourably with those of azidothymidine given intraperitoneally at 30 mg/kg/day. Western blots performed on splenic tissue from control and treated animals indicated that glutamine depletion prevented readthrough of an amber codon at the gag-pol junction, stopping translation of viral mRNA at that point. Treatment of RLV-infected animals with PGA resulted in nearly a 200% increase in mean survival time even when therapy was initiated late in the course of the disease. To our knowledge, this is the first demonstration that a nutrient required for viral replication can be enzymically depleted in vivo to inhibit viral replication.
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PMID:Inhibition of mouse retroviral disease by bioactive glutaminase-asparaginase. 170 10

Glutamine(asparagine)ase from Ps. boreopolis 526 has an antineoplastic effect on lymphoid leukemia P-388. The enzyme half-life in the mouse serum is 8.5 hours. Glutamine(asparagine)ase has no cross-antigenicity with L-asparaginase from E. coli (Bayer, FRG). Specific antibodies against L-asparaginase (Bayer, FRG) do not influence the activity of glutamine(asparagine)ase.
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PMID:[Biological properties of glutamin-(asparagin-)ase from Pseudomonas boreopolis 526]. 373 May 98

In a series of four experiments, asparaginase and glutaminase activity was measured in liver and kidney tissue of 7- to 19-day-old male broiler chicks. In Experiment 1, chicks were fed purified amino acid diets with 14.8 and 44.6% protein equivalents (PE) with 1, 3, or 5% added sodium bicarbonate. In Experiments 2, 3, and 4 the chicks were fed a 23% protein basal control diet, basal diet containing 5% ammonium chloride, and basal diet containing 5% ammonium chloride with 5 or 10% sodium bicarbonate, asparagine, or glutamine. In Experiments 2 and 4 the chicks were also fed 25, 50, or 75% protein-isolated soy-purified diets. The 44.6% PE diet increased liver and kidney asparaginase activity in chicks as compared to chicks fed a 14.8% PE diet. The addition of sodium bicarbonate to the 44.6% PE amino acid diet decreased the kidney asparaginase activity equivalent to kidney asparaginase activity of chicks fed the 14.8% PE diet. Asparaginase activity increased 4-fold in the kidneys of chicks fed the 23% protein basal diet containing 5% ammonium chloride and the pH of the urine from the chicks was 4.9. Chicks fed basal diets with 5% ammonium chloride plus 10% sodium bicarbonate or asparagine had the same kidney asparaginase activity and urine pH as chicks fed the 23% protein basal control diet. Glutamine added to chick diets containing 5% ammonium chloride did not decrease the kidney asparaginase activity or the urine acidity. Liver asparaginase activity was not increased in acidotic chicks fed diets with 5% ammonium chloride. The asparaginase activity of liver and kidney tissue were both significantly increased in chicks fed 75% protein-isolated soy purified diets and the pH of their urine was 5.6. The increase in liver asparaginase of chicks fed 75% protein or 44.5% PE diets was probably due to an endocrine gluconeogenic response producing increased catabolism of the majority of amino acids. The increase in kidney asparaginase of chicks fed 75% protein, 44.5% PE diets, and 23% protein basal diets with 5% ammonium chloride was primarily related to metabolic acidosis. Phosphate-dependent glutaminase (PDG) activity was localized in chick kidney mitochondria and was heat sensitive (55 C for 30 sec). The phosphate-independent glutaminase (PIG) activity was primarily localized in chick kidney mitochondria but was stable to a temperature of 55 C for 30 sec.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Asparagine and glutamine metabolism in chicks. 632 68

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

Cell shrinkage and loss of cell viability by apoptosis have been examined in cultured CD95(Fas/Apo-1)-expressing leukemia-derived CEM and HL-60 cells subjected to acute deprivation of glutamine, a major compatible osmolyte engaged in cell volume control. Glutamine deprivation-mediated cell shrinkage promoted a ligand-independent activation of the CD95-mediated apoptotic pathway. Cell transfection with plasmids expressing FADD-DN or v-Flip viral proteins pointed to a functional clustering of CD95 receptors at the cell surface with activation of the 'extrinsic pathway' caspase cascade. Accordingly, cell shrinkage did not induce apoptosis in CD95 receptor-negative lymphoma L1210 cells. Replacement of glutamine with surrogate compatible osmolytes counteracted cell volume decrement and protected the CD95-expressing cells from apoptosis. A glutamine deprivation-dependent cell shrinkage with activation of the CD95-mediated pathway was also observed when asparaginase was added to the medium. Asparagine depletion had no role in this process. The cell-size shrinkage-dependent apoptosis induced by glutamine restriction in CD95-expressing leukemic cells may therefore be of clinical relevance in amidohydrolase enzyme therapies.
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PMID:Glutamine deprivation-mediated cell shrinkage induces ligand-independent CD95 receptor signaling and apoptosis. 1159 98

Net balances of amino acids were constructed for stages of development of a leaf of white lupin (Lupinus albus L.) using data on the N economy of the leaf, its exchanges of amino acids through xylem and phloem, and net changes in its soluble and protein-bound amino acids. Asparagine, aspartate, and gamma-aminobutyrate were delivered to the leaf in excess of amounts consumed in growth and/or phloem export. Glutamine was supplied in excess until full leaf expansion (20 days) but was later synthesized in large amounts in association with mobilization of N from the leaf. Net requirements for glutamate, threonine, serine, proline, glycine, alanine, valine, isoleucine, leucine, tyrosine, phenylalanine, histidine, lysine, and arginine were met mainly or entirely by synthesis within the leaf. Amides furnished the bulk of the N for amino acid synthesis, asparagine providing from 24 to 68%. In vitro activity of asparaginase (EC 3.5.1.1) exceeded that of asparagine:pyruvate aminotransferase (EC 2.6.1.14) during early leaf expansion, when in vivo estimates of asparagine metabolism were highest. Thereafter, aminotransferase activity greatly exceeded that of asparaginase. Rates of activity of one or both asparagine-utilizing enzymes exceeded estimated rates of asparagine catabolism throughout leaf development. In vitro activities of glutamine synthetase (EC 6.3.1.2) and glutamate synthase (EC 1.4.7.1) were consistently much higher than that of glutamate dehydrogenase (EC 1.4.1.3), and activities of the former two enzymes more than accounted for estimated rates of ammonia release in photorespiration and deamidation of asparagine.
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PMID:Amino Acid transport and metabolism in relation to the nitrogen economy of a legume leaf. 1666 17


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