Disease relevance of iaaA

• We describe the expression, purification, and biochemical characterization of two homologous enzymes, with amidohydrolase activities, of plant (Lupinus luteus potassium-independent asparaginase, LlA) and bacterial (Escherichia coli, ybiK/spt/iaaA gene product, EcAIII) origin [1].
• The findings were consistent with reports that L-asparaginase is effective in suppressing cellular immunity and inducing remission in patients with acute lymphocytic leukemia, mainly a non-B-cell disease [2].
• 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 [3].
• Purification and characterization of L-asparaginase with anti-lymphoma activity from Vibrio succinogenes [4].
• L-Asparaginase-induced diabetes mellitus in rabbits [5].

High impact information on iaaA

• T-cells were 800-2,000 times more sensitive to Escherichia coli L-asparaginase than were B-cells [2].
• The cytotoxic effects of a high concentration of L-asparaginase on B-cells were not related to the hydrolysis of L-asparagine but were due to heat-labile and heat-resistant substances in the enzyme [2].
• The minimal plasma level of L-asparaginase necessary to deplete CSF asparagine in both species was 0.1 IU/ml [6].
• In order to better define the relationship between L-asparaginase administration and cerebrospinal fluid (CSF) asparagine levels, L-asparaginase and asparagine were measured in the CSF of rhesus monkeys following intrathecal and i.v. administration [6].
• L-asparaginase pharmacokinetics and asparagine levels in cerebrospinal fluid of rhesus monkeys and humans [6].

Chemical compound and disease context of iaaA

• Weekly polyethylene glycol conjugated L-asparaginase compared with biweekly dosing produces superior induction remission rates in childhood relapsed acute lymphoblastic leukemia: a Pediatric Oncology Group Study [7].
• Following intrathecal injection, the enzyme activity of Escherichia coli L-asparaginase in the CSF demonstrated a more rapid terminal half-life than did that of 111In-labeled diethylenetriaminepentaacetic acid, a marker of CSF bulk flow [4 +/- 0.7 (S.D.) hr versus 5.8 +/- 0.2 hr] [6].
• The L-asparagine analogue 5-diazo-4-oxo-L-[5-14C]norvaline binds irreversibly to the active site of Escherichia coli L-asparaginase [8].
• Reductive coupling with sodium cyanoborhydride has been used with lactose and N-acetylneuraminyl lactose to prepare glycosylated Escherichia coli L-asparaginase [9].
• The effect of E. coli L-asparaginase on oral glucose tolerance and insulin release in man [10].

Biological context of iaaA

• Crystallization and preliminary crystallographic studies of a new L-asparaginase encoded by the Escherichia coli genome [11].
• Structure of peptide from active site region of Escherichia coli L-asparaginase [8].
• Glycosylation of Escherichia coli L-asparaginase [9].
• To investigate this fundamental difference in the regulation of L-asparaginase II expression in S. enterica, the ansB gene was cloned and the nucleotide sequence of the promoter region determined [12].
• Although the addition of L-glutamine to the culture appeared to prevent cell death caused by L-asparaginase, it did not restore the ability of the cells to proliferate [13].

Anatomical context of iaaA

• These data indicate that systemic L-asparaginase therapy may be a feasible means of treating central nervous system involvement in patients with acute lymphoblastic leukemia and that there is no therapeutic advantage to using intrathecal L-asparaginase [6].
• The immunogenicity of the modified enzyme was substantially reduced because mouse antiserum to it showed no significant increase in hemagglutinin titer of L-asparaginase-coated sheep red blood cells [14].
• Direct long-term effects of L-asparaginase on rat and human pancreatic islets [15].
• L-asparaginase bound to collagen membranes: effect of glutaraldehyde crosslinking on stabilization of catalytic activity [16].
• L-asparaginase is a promising agent for the treatment of NK/T cell lymphoma [17].

Associations of iaaA with chemical compounds

• Intravenous regular insulin decreased glucose levels in L-asparaginase-treated animals at 3 h by only 7.7 +/- 3.2%, while it decreased them in controls by 34.0 +/- 6.7% (P less than 0.0025) [5].
• Role of Glutamine Depletion in Directing Tissue-specific Nutrient Stress Responses to L-Asparaginase [18].
• Chemical modification of L-asparaginase with comb-shaped copolymer of poly(ethylene glycol) derivative and maleic anhydride [19].
• Alterations in hemostasis have frequently been observed in patients with leukemia, and thrombotic events are well documented in patients receiving L-asparaginase (ASP) as a single agent or in combination with vincristine, prednisone (sometimes complemented by an anthracycline) [20].
• Stabilization of L-asparaginase toward heat, urea, and acidity was caused by modifying the enzyme with activated PM13 and PM100 [21].

Analytical, diagnostic and therapeutic context of iaaA

• In CALGB study 8811 (Blood 1995; 85: 2025-2037), 197 adults were scheduled to receive 14 doses of Escherichia coil L-asparaginase (6000 U/m2 SC) during 7 of the first 12 weeks of chemotherapy [22].
• This study shows that the antigenicity of Erwinia chrysanthemi L-asparaginase can be reduced by site-directed mutagenesis [23].
• The overall rate of event-free survival was lower in patients treated with L-asparaginase than in other patients (P = 0.06); estimated 3-year rates were 72% (95% confidence interval, 55-89%) and 87.2% (78-96%), respectively [24].
• Erwinia chrysanthemi L-asparaginase: epitope mapping and production of antigenically modified enzymes [23].
• The Escherichia coli gene ansB, encoding the chemotherapeutic enzyme L-asparaginase II, has been cloned, using a strategy based on the polymerase chain reaction, and sequenced [25].

References