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)

Seventy-five rats, divided into five groups, were given D-aspartic acid (D-Asp), L-Asp and D + L-Asp in ratio 1/1 or 1/2 for one week. The body weight, food and fluid intakes, and rectal temperature of the rats received D-Asp or D + L-Asp in 1/1 ratio significantly decreased. The decrease in rectal temperature was antagonized by naloxone. L-Asp given together with D-Asp in 1/2 ratio prevented D-Asp-caused decrease in body weight, food and fluid intakes, and rectal temperature. Although D-amino acids, as antipeptidases have some effects through endorphinergic systems, D-Asp (an inhibitor of L-asparaginase) seems to act at the level of L-asparaginase presumably by increasing the level of endorphins since L-Asp antagonizes the inhibitory effect of both D-Asp and morphine.
Pol J Pharmacol Pharm
PMID:Antagonistic effect of L-aspartic acid on decrease in body weight, and food and fluid intake, and naloxone reversible rectal temperature depression caused by D-aspartic acid. 718 48

Two cases of hyperglycemia complicating therapy of childhood ALL with the use of L-asparaginase are described. Both patients required insulin administration. The relationship between L-aspa therapy and clinical manifestation of hyperglycemia seems to indicate that this could be the side effects of the drug.
Acta Haematol Pol 1995
PMID:[Hyperglycemia as a side effect of using L-asparaginase in children with acute lymphoblastic leukemia (ALL]. 774 69

The treatment of the acute lymphoblastic leukemia in childhood includes frequent administration of L-asparaginase by intravenous route. L-asparaginase is an enzyme produced by E. coli and Erwinia chrysanthemi strains. Adverse reactions produced by L-asparaginase are numerous, and pancreatitis is being the most severe. Children with the acute lymphoblastic leukemia were followed up for 2 years. Hyperglycaemia and glycosuria were noted in 10% of them resulting in L-asparaginase cessation or replacement by less toxic agents. The acute pancreatitis was produced in 8% of the patients, and was treated typically.
Pol Tyg Lek
PMID:[Acute pancreatitis in children with acute lymphoblastic leukemia treated with L-asparaginase]. 780 58

A conservative and apparently harmless A176V mutation in intracellular S. cerevisiae L-asparaginase (ScerAI) completely abolishes the enzyme activity. Sequence and structural comparisons with type II bacterial L-asparaginases show that the mutated residue is in a very conservative region and plays a vital role in the cohesion of functional tetramers of these enzymes through participation in side-chain...main-chain (Ser) Oy...O (Ala) hydrogen bonds across the tetramer interface. The fact that bacterial L-asparaginases of type I show less conservation in this region suggests that they may have different quaternary structure while adopting the subunit fold and intimate dimer architecture of type II enzymes. A comparison of all available sequences of microbial L-asparaginases confirms that separate intra- and extra-cellular enzymes evolved in prokaryotes and eukaryotes independently. However, an analysis of the available complete genome sequences reveals a surprising fact that Haemophilus influenzae possesses only a type II asparaginase while the archaebacterium Methanococcus jannaschii has a type I gene, but not a type II.
Acta Biochim Pol 1997
PMID:Why a "benign" mutation kills enzyme activity. Structure-based analysis of the A176V mutant of Saccharomyces cerevisiae L-asparaginase I. 951 60

Periplasmic Escherichia coli L-asparaginase II with Y25F mutation in the active-site cavity has been obtained by recombinant techniques. The protein was crystallized in a new hexagonal form (P6(5)22). Single crystals of this polymorph, suitable for X-ray diffraction, were obtained by vapor diffusion using 2-methyl-2,4-pentanediol as precipitant (pH 4.8). The crystals are characterized by a = 81.0, c = 341.1 A and diffract to 2.45 A resolution. The asymmetric unit contains two protein molecules arranged into an AB dimer. The physiologically relevant ABA'B' homotetramer is generated by the action of the crystallographic 2-fold axis along [1, -1, 0]. Kinetic studies show that the loss of the phenolic hydroxyl group at position 25 brought about by the replacement of Y with F strongly impairs kcat without significantly affecting Km.
Acta Biochim Pol 2000
PMID:Preliminary crystallographic studies of Y25F mutant of periplasmic Escherichia coli L-asparaginase. 1131 Sep 79

Asparaginases catalyze the hydrolysis of asparagine to aspartic acid and ammonia. Enzymes with asparaginase activity play an important role both in the metabolism of all living organisms as well as in pharmacology. The main goal of this paper is to attempt a classification of all known enzymes with asparaginase activity, based on their amino acid sequences. Some possible phylogenetic consequences are also discussed using dendrograms and structural information derived from crystallographic studies.
Acta Biochim Pol 2001
PMID:Sequence analysis of enzymes with asparaginase activity. 1199

The small angle X-ray scattering (SAXS) pattern of the homotetrameric asparaginase II from Escherichia coli was measured in solution in conditions resembling those in which its crystal form was obtained and compared with that calculated from the crystallographic model. The radius of gyration measured by SAXS is about 5% larger and the maximum dimension in the distance distribution function about 12% larger than the corresponding value calculated from the crystal structure. A comparison of the experimental and calculated distance distribution functions suggests that the overall quaternary structure in the crystal and in solution are similar but that the homotetramer is less compact in solution than in the crystal.
Acta Biochim Pol 2002
PMID:A comparison between the crystal and solution structures of Escherichia coli asparaginase II. 1236 93

L-asparaginase and glucocorticosteroides are the main drugs used in the first-line treatment in children with acute lymphoblastic leukaemia. One of the observed side effects in the increase of serum level of triglycerides is synergistic manner. The paper describes two children with acute lymphoblastic leukaemia. In these patients we could observe remarkable hypertriglyceridemia, and hypercholesterolaemia with the increase of LDL-cholesterol after applying high doses of L-asparaginase and glucocorticosteroids simultaneously. The above-mentioned disorders were transient. In the analysis of the possible reasons of this pathology we took into consideration family predispositions, the transient deficit of lipoprotein lipase induced by L-asparaginase, improper diet and hyperthyroidismus.
Pol Merkur Lekarski 2003 Sep
PMID:[Iatrogenic hyperlipidemia after l-asparaginase and glucocorticoid treatment in two children with acute lymphoblastic leukemia]. 1467 52

L-asparaginase is a hydrolase that catalyzes the conversion of L-asparagine--an endogenous amino acid necessary for the function of some neoplastic cells, such as lymphoblasts. In most human cells deficiency of L-asparagine can be compensated by alternative synthesis pathway through which L-asparagine is produced from aspartic acid and glutamine by asparagine synthethase. Depletion of L-asparagine from plasma by L-asparaginase results in inhibition of RNA and DNA synthesis with the subsequent blastic cell apoptosis. Owing to the unique anti-cancer mechanism of action, L-asparaginase has been introduced to the multi drug chemotherapy in children and adults with acute lymphoblastic leukemia, which has contributed to significant improvement of therapy outcomes and to achieve complete remission in about 90% of patients. Notwithstanding its high therapeutic efficacy, L-asparaginase can increase the risk of thrombosis. Inhibition of protein synthesis causes most complications observed during treatment with a native and pegylated form of L-asparaginase, including impaired functions of liver, kidneys or central nervous system. Thrombotic events occur as a result of inhibited synthesis of anticoagulant proteins (mainly antithrombin). Coagulopathy has been observed in 1.1-4% of patients treated with the pegylated L-asparaginase and in 2.1-15% of those receiving its native form. In this paper approaches to optimize the therapy with L-asparaginase have been discussed.
Pol Arch Med Wewn 2008 Nov
PMID:Use of L-asparaginase in acute lymphoblastic leukemia: recommendations of the Polish Adult Leukemia Group. 1914 May 71

Marine actinomycetes were isolated from sediment samples collected from Pitchavaram mangrove ecosystem situated along the southeast coast of India. Maximum actinomycete population was noted in rhizosphere region. About 38% of the isolates produced L-asparaginase. One potential strain KUA106 produced higher level of enzyme using tryptone glucose yeast extract medium. Based on the studied phenotypic characteristics, strain KUA106 was identified as Streptomyces parvulus KUA106. The optimization method that combines the Plackett-Burman design, a factorial design and the response surface method, which were used to optimize the medium for the production of L-asparaginase by Streptomycetes parvulus. Four medium factors were screened from eleven medium factors by Plackett-Burman design experiments and subsequent optimization process to find out the optimum values of the selected parameters using central composite design was performed. Asparagine, tryptone, d) extrose and NaCl components were found to be the best medium for the L-asparaginase production. The combined optimization method described here is the effective method for screening medium factors as well as determining their optimum level for the production of L-asparaginase by Streptomycetes parvulus KUAP106.
Pol J Microbiol 2011
PMID:Screening of Actinomycetes from mangrove ecosystem for L-asparaginase activity and optimization by response surface methodology. 2218 28


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