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)

After oral or parenteral administration of chemotherapeutic agents, these drugs are transported to the tissues by the blood in different fractions: plasma water, plasma proteins or cells. Erythrocytes may play an important role in the storage, transport and metabolism of chemotherapeutic agents. Anthracyclines, ifosfamide and its metabolites, and topoisomerase I and I/II inhibitors are incorporated in red blood cells. They may be transported to the tumour tissue and mobilised from the erythrocyte by different active or passive transport mechanisms. Erythrocytes may also be used as carriers for drugs such as asparaginase. This leads to a decreased toxicity profile. Finally, it has been shown that red blood cells are important in the transport and metabolism of mercaptopurine. The erythrocyte concentration of mercaptopurine has a prognostic value in the treatment of childhood acute lymphoblastic leukemia. In this review, the role of red blood cells for various anticancer drugs is further discussed.
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PMID:Role of red blood cells in pharmacokinetics of chemotherapeutic agents. 1288 86

In the present study, antileukemic enzyme L-asparaginase (ASNase) was encapsulated into poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) nanocapsules in order to decrease the immunogenicity and toxicity of the enzyme and to increase its in vivo half life in mice. Nanocapsules were prepared by water-in-oil-in-water approach and each phase was changed systematically. By changing the pH of the w(2) phase to the isolelectric point of L-ASNase, the encapsulation efficiency was increased from 23.7% to 28.0%. Also, modification of ASNase with PEG(2) increased the encapsulation efficiency from 23.7% to 27.9% and protected the enzyme against denaturation. Combination of the various optima enabled a substantial increase in the activity (0.074-0.429 U/mg nanocapsule). The enzyme activity in the blood due to unmodified PHBV nanocapsules dropped to 38% of its initial value 4 h after injection. When the same sample was tested for the enzyme content in the circulation by using the radio-labeled enzyme a much lower enzyme (30% of initial) could be detected after a shorter time (3 h). The PHBV nanocapsules with heparin conjugated on their surface had a longer presence in the circulation than unmodified PHBV nanocapsules. After 6 h, around 50% of the enzyme was still present in the blood. Radioactivity measurements using the same sample showed a sharp decrease in enzyme amount in the circulation in the early stages. However, radioactivity was still detectable at the eighth hour. No adverse effects and symptoms of anaphylaxis were observed upon injection of encapsulated ASNase-PHBV nanocapsules to mice i.v. through the tail vein.
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PMID:In vivo half life of nanoencapsulated L-asparaginase. 1534 52

L-asparaginase (ASNase) is one basic drug in the treatment of acute lymphoblastic leukemia (ALL). Because its half-life time is too short and it is easy to arouse allergic reaction, use in practical clinic is considerably limited. Silk fibroin (SF) with different molecular mass from 40 to 120 kDa is a natural biocompatible protein and could be used as a novel bioconjugate for enzyme modification to overcome its usual shortcomings mentioned above. When the enzyme was bioconjugated covalently with the water-soluble fibroin by glutaraldehyde, the enzyme kinetic properties and immune characteristics in vivo of the resulting silk fibroin-L-asparaginase (SF-ASNase) bioconjugates were investigated in detail. The results show that the modified ASNase was characterized by its higher residual activity (nearly 80%), increased heat and storage stability and resistance to trypsin digestion, and its longer half-life (63 h) than that of intact ASNase (33 h). The abilities of intact and modified ASNases to arouse allergic reaction are 2(4) and 2(1) antibody titers, respectively. Bioconjugation of silk fibroin significantly helps to reduce the immunogenicity and antigenicity of the enzyme. The apparent Michaelis constants of the modified ASNase (K(m(app))=0.844 x 10(-3)mol L(-1)) was approximately six times lower than that of enzyme alone, which suggests that the affinity of the enzyme to substrate l-asparagine elevated when bioconjugated covalently with silk fibroin. SF-ASNase bioconjugates could overcome the common shortcomings of the native form. Therefore, the modified ASNase coupled with silk fibroin has the potential values of being studied and developed as a new bioconjugate drug.
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PMID:Synthesis, characterization and immunogenicity of silk fibroin-L-asparaginase bioconjugates. 1610 67

AnsA is the cytoplasmic asparaginase from Escherichia coli involved in intracellular asparagine utilization. Analytical ultracentifugation and X-ray crystallography reveal that AnsA forms a tetrameric structure as a dimer of two intimate dimers. Kinetic analysis of the enzyme reveals that AnsA is positively cooperative, displaying a sigmoidal substrate dependence curve with an [S](0.5) of 1 mM L-asparagine and a Hill coefficient (n(H)) of 2.6. Binding of L-asparagine to an allosteric site was observed in the crystal structure concomitant with a reorganization of the quarternary structure, relative to the apo enzyme. The carboxyl group of the bound asparagine makes salt bridges and hydrogen bonds to Arg240, while the N(delta2) nitrogen interacts with Thr162. Mutation of Arg240 to Ala increases the [S](0.5) value to 5.9 mM, presumably by reducing the affinity of the site for L-asparagine, although the enzyme retains cooperativity. Mutation of Thr162 to Ala results in an active enzyme with no cooperativity. Transmission of the signal from the allosteric site to the active site appears to involve subtle interactions at the dimer-dimer interface and relocation of Gln118 into the vicinity of the active site to position the probable catalytic water molecule. These data define the structural basis for the cooperative regulation of the intracellular asparaginase that is required for proper functioning within the cell.
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PMID:Crystal structure and allosteric regulation of the cytoplasmic Escherichia coli L-asparaginase I. 1745 45

The field study was conducted to evaluate the effect of municipal solid waste compost (MSWC) as a soil amendment on L-asparaginase (LA) and L-glutaminase (LG) activities. Experiments were conducted during the wet seasons of 1997, 1998 and 1999 on rice grown under a submerged condition, at the Agriculture Experimental Farm, Calcutta University at Baruipur, West Bengal, India. The treatments consisted of control, no input; MSWC, at 60 Kg N ha(- 1); well-decomposed cow manure (DCM), at 60 Kg N ha(- 1); MSWC (30 Kg N ha(- 1)) + Urea (U) (30 Kg N ha(- 1)); DCM (30 Kg N ha(- 1)) + U (30 Kg N ha(- 1)) and Fertilizer, (at 60:30:30 NPK kg ha(- 1)) through urea, single superphosphate and muriate of potash respectively). LA and LG activities alone and their ratio with organic-C (ratio index value, RIV), straw and grain yield were higher in DCM than MSWC-treated soils, due to higher amount of biogenic organic materials like water-soluble organic carbon, carbohydrate and mineralizable nitrogen in the former. The studied parameters were higher when urea was integrated with DCM or MSWC, compared to their single applications. The heavy metals in MSWC did not detrimentally influence the above-measured activities of soil. In the event of long term MSWC application, changes in soil quality parameters should be monitored regularly, since heavy metals once entering into soil persist over a long period.
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PMID:L-asparaginase and L-glutaminase activities in submerged rice soil amended with municipal solid waste compost and decomposed cow manure. 1756 68

Two approaches have been used to produce universal group O donor red blood cells (RBCs) from groups A, B, and AB RBCs. The first involves cleavage of the terminal immunodominant sugars from carbohydrate chains on the RBC membrane, using specific enzymes, to produce so-called enzyme-converted group O (ECO) RBCs. ECO RBCs have been produced from whole units of B RBCs and transfused successfully to humans. Group A RBCs (especially A(1) RBCs) have been more difficult. New sources of enzymes have produced ECO RBCs from A(1) and A(2) RBCs that do not react with powerful monoclonal anti-A. Unfortunately, there are still problems encountered with polyclonal human antibodies (i.e. cross-matching). The second approach interferes with an antibody reaching its specific antigen on the RBC membrane by bonding polyethylene glycol (PEG) to the RBC. PEG will attract water molecules, yielding a combination that may block most RBC antigens, including A and B antigens. Initial excitement generated by preliminary reports of the possibility of producing 'stealth' PEG-RBCs were tempered by the findings of in vitro serological problems and possible reduced in vivo RBC survival. Many of these problems were solved, but recent findings that PEG is immunogenic in animals and humans, and that PEG antibodies can shorten the survival of PEG-RBCs (in rabbits) and pegylated proteins (e.g. PEG-asparaginase) in humans, are disturbing, suggesting that 'stealth' RBCs may never become a reality.
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PMID:Modulating the red cell membrane to produce universal/stealth donor red cells suitable for transfusion. 1803 87

Asparaginase (Elspar) is used in the treatment of acute lymphoblastic leukemia. It depletes plasma asparagine and glutamine, killing leukemic lymphoblasts but also causing immunosuppression. The objective of this work was to assess whether supplementing the diet with glutamine modifies the effect of asparaginase on normal lymphocyte populations in the spleen, thymus, and bone marrow. Mice consuming water ad libitum with or without alanyl-glutamine dipeptide (AlaGln; 0.05 mol/L) were injected once daily with 0 or 3 international units/g body weight Escherichia coli L-asparaginase for 7 d. Tissue expression of specific immune cell surface markers was analyzed by flow cytometry. Asparaginase reduced B220+ and sIgM+ cells in the bone marrow (P < 0.05) and diminished total cell numbers in thymus (-42%) and spleen (-53%) (P < 0.05). In thymus, asparaginase depleted double positive (CD4+ CD8+) and single positive (CD4+ CD8-, CD4-CD8+) thymocytes by over 40% (P < 0.05). In spleen, asparaginase reduced CD19+ B cells to 33% of controls and substantially depleted the CD4+ and CD8+ T cell populations. CD11b-expressing leukocytes were reduced by 50% (P < 0.05). Consumption of AlaGln did not lessen the effects of asparaginase in bone marrow or thymus but mitigated cellular losses in the CD4+, CD8+, and CD11b+ populations in spleen. AlaGln also blunted the increase in eukaryotic initiation factor 2 (eIF2) phosphorylation by asparaginase in spleen, whereas eIF2 phosphorylation did not change in thymus in response to asparaginase or AlaGln. In conclusion, asparaginase reduces maturing populations of normal B and T cells in thymus, bone marrow, and spleen. Oral consumption of AlaGln mitigates metabolic stress in spleen, supporting the peripheral immune system and cell-mediated immunity during asparaginase chemotherapy.
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PMID:Alanyl-glutamine consumption modifies the suppressive effect of L-asparaginase on lymphocyte populations in mice. 1820 1

The crystal structures of Erwinia carotovora L-asparaginase complexed with L-aspartate and L-glutamate were determined at 1.9 and 2.2 A, respectively, using the molecular-replacement method and were refined to R factors of about 21% in both cases. The positions of the ligands in the active site were located. A comparison of the new structures with the known structures of Escherichia coli L-asparaginase and Er. chrysanthemi L-asparaginase was performed. It was found that the arrangement of the ligands practically coincides in all three enzymes. The peculiarities of the quaternary structure of the enzyme, the possible role of water molecules in the enzyme action and the conformational changes during the catalyzed reaction are discussed.
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PMID:Three-dimensional structures of L-asparaginase from Erwinia carotovora complexed with aspartate and glutamate. 1832 19

Asparaginase, an enzyme that hydrolyzes asparagine to aspartic acid, presents a potentially very effective means for reducing acrylamide formation in foods via removal of the precursor, asparagine, from the primary ingredients. An extracellular asparaginase amenable to industrial production was cloned and expressed in Aspergillus oryzae . This asparaginase was tested in a range of food products, including semisweet biscuits, ginger biscuits, crisp bread, French fries, and sliced potato chips. In dough-based applications, addition of asparaginase resulted in reduction of acrylamide content in the final products of 34-92%. Enzyme dose, dough resting time, and water content were identified as critical parameters. Treating French fries and sliced potato chips was more challenging as the solid nature of these whole-cut products limits enzyme-substrate contact. However, by treating potato pieces with asparaginase after blanching, the acrylamide levels in French fries could be lowered by 60-85% and that in potato chips by up to 60%.
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PMID:Evaluating the potential for enzymatic acrylamide mitigation in a range of food products using an asparaginase from Aspergillus oryzae. 1938 39

Increasing proportions of coal fly ash were co-composted with municipal green waste to produce manufactured soil for landscaping use. Only the 100% green waste treatment reached a thermophilic composting phase (50 degrees C) which lasted for 6 days. The 25% and 50% ash treatments reached 36-38 degrees C over the same period while little or no self-heating occurred in the 75% and 100% ash treatments. Composted green waste had a low bulk density and high total and macro-porosity. Addition of 25% ash to green waste resulted in a 75% increase in available water holding capacity. As the proportions of added ash in the composts increased, the organic C, soluble C, microbial biomass C, basal respiration and activities of beta-glucosidase, L-asparaginase, alkali phosphatase and arylsulphatase enzymes in the composted products all decreased. It could be concluded that addition of fly ash to green waste at a proportion higher than 25% did not improve the quality parameters of manufactured soil.
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PMID:Chemical, microbial and physical properties of manufactured soils produced by co-composting municipal green waste with coal fly ash. 1953 64


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