Bacterial asparaginase (L-Asparaginase amidohydrolase, E.C. 3.5.1.1) is a selective and highly effective chemotherapeutic agent extensively used over the world in first-line treatment of acute lymphoblastic leukemia (ALL), Hodgkin disease, acute myelocytic leukemia, acute melanomonocytic leukemia, chronic lymphocytic leukemia, lymphosarcoma, reticlesarcoma and melanosarcoma (Verma et al., 2007)...

Bacterial L-asparaginases, which are widely used in the antitumor therapy, act only as homotetramers, because their active sites are located at the interface between the subunits of the enzyme. Since salt bridges substantially stabilize L-asparaginase tetramers, we have supposed that oligomerization of bacterial L-asparaginase is a high-avidity process. This assumption was proved by bioinformat...

Asparaginase is an important antileukemic agent extensively used worldwide but the intrinsic glutaminase activity of this enzymatic drug is responsible for serious life threatening side effects. Hence, glutaminase free asparaginase is much needed for upgradation of therapeutic index of asparaginase therapy. In the present study, glutaminase free asparaginase produced from Enterobacter cloacae w...

53 The anti-leukemic agent asparaginase triggers the amino acid response (AAR) in liver by 54 activating the eukaryotic initiation factor 2 (eIF2) kinase GCN2. To explore the 55 mechanism by which AAR induction is necessary to mitigate hepatic lipid accumulation 56 and prevent liver dysfunction during continued asparaginase treatment, wild-type and 57 Gcn2 null mice were injected once daily wit...

Hypersensitivity reactions are the most frequent dose-limiting adverse reactions to Escherichia coli-derived asparaginase in pediatric acute lymphoblastic leukemia (ALL) patients. The aim of the present study was to identify associations between sequence-based Human Leukocyte Antigen Class II region alleles and asparaginase hypersensitivity in a Hungarian ALL population. Four-digit typing of HL...

The relapse rate in childhood acute lymphoblastic leukemia (ALL) is approximately 30% but few reinduction regimens have investigated the intensive use of polyethylene glycol Escherichia coli asparaginase (PEG-Asp). Therefore, we assessed the pharmocokinetics and efficacy of PEG-Asp in this setting. Children with B-precursor ALL, in first marrow and/or extramedullary relapse were eligible. Reind...

Enzyme L-asparaginase (L-asparagines amidohydrolase EC 3.5.1.1) has the physiological function of hydrolyzing amide group of the side chain in Lasparagine to produce L-aspartate and ammonia. This spectacular property of the enzyme is utilized in chemotherapeutic treatment of certain kinds of lymphoblastic malignancies, mainly in acute lymphoblastic leukaemia (ALL) and lympho-sarcoma for nearly ...

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 additio...

A species of Streptomyces, Streptomyces ginsengisoli, a river isolate, was evaluated for production of an enzyme, L-asparaginase, with multiple functions mainly anticancer activity. The actinomycete was subjected to submerged fermentation by "shake flask" method. The quantity of L-asparaginase produced was estimated as 3.23 μ mol/mL/min. The effect of various culture conditions on L-asparaginas...

In early studies using high dosages of Escherichia coli asparaginase (10 doses of 1000 ID/kg each) for the treatment of acute lymphoblastic leukemia, hepatotoxicity was a major com plication of therapy. Biochemical evidence of hepatic dysfunction occurred in 75% of patients during the first 2 weeks of treatment. Currently, the use of lower dosages of E. coli asparaginase (three doses of 6000 ID...