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

---

Query: EC:3.5.1.1 (asparaginase)
2,695 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Potentially toxic acrylamide is largely derived from heat-induced reactions between the amino group of the free amino acid asparagine and carbonyl groups of glucose and fructose in cereals, potatoes, and other plant-derived foods. This overview surveys and consolidates the following dietary aspects of acrylamide: distribution in food originating from different sources; consumption by diverse populations; reduction of the acrylamide content in the diet; and suppression of adverse effects in vivo. Methods to reduce adverse effects of dietary acrylamide include (a) selecting potato, cereal, and other plant varieties for dietary use that contain low levels of the acrylamide precursors, namely, asparagine and glucose; (b) removing precursors before processing; (c) using the enzyme asparaginase to hydrolyze asparagine to aspartic acid; (d) selecting processing conditions (pH, temperature, time, processing and storage atmosphere) that minimize acrylamide formation; (e) adding food ingredients (acidulants, amino acids, antioxidants, nonreducing carbohydrates, chitosan, garlic compounds, protein hydrolysates, proteins, metal salts) that have been reported to prevent acrylamide formation; (f) removing/trapping acrylamide after it is formed with the aid of chromatography, evaporation, polymerization, or reaction with other food ingredients; and (g) reducing in vivo toxicity. Research needs are suggested that may further facilitate reducing the acrylamide burden of the diet. Researchers are challenged to (a) apply the available methods and to minimize the acrylamide content of the diet without adversely affecting the nutritional quality, safety, and sensory attributes, including color and flavor, while maintaining consumer acceptance; and (b) educate commercial and home food processors and the public about available approaches to mitigating undesirable effects of dietary acrylamide.
...
PMID:Review of methods for the reduction of dietary content and toxicity of acrylamide. 1862 52

Bacterial L-asparaginases are enzymes that catalyze the hydrolysis of l-asparagine to aspartic acid. For the past 30 years, these enzymes have been used as therapeutic agents in the treatment of acute childhood lymphoblastic leukemia. Their intrinsic low-rate glutaminase activity, however, causes serious side-effects, including neurotoxicity, hepatitis, coagulopathy, and other dysfunctions. Erwinia carotovora asparaginase shows decreased glutaminase activity, so it is believed to have fewer side-effects in leukemia therapy. To gain detailed insights into the properties of E. carotovora asparaginase, combined crystallographic, thermal stability and cytotoxic experiments were performed. The crystal structure of E. carotovoral-asparaginase in the presence of L-Asp was determined at 2.5 A resolution and refined to an R cryst of 19.2 (R free = 26.6%) with good stereochemistry. Cytotoxicity measurements revealed that E. carotovora asparaginase is 30 times less toxic than the Escherichia coli enzyme against human leukemia cell lines. Moreover, denaturing experiments showed that E. carotovora asparaginase has decreased thermodynamic stability as compared to the E. coli enzyme and is rapidly inactivated in the presence of urea. On the basis of these results, we propose that E. carotovora asparaginase has limited potential as an antileukemic drug, despite its promising low glutaminase activity. Our analysis may be applicable to the therapeutic evaluation of other asparaginases as well.
...
PMID:Structural and functional insights into Erwinia carotovora L-asparaginase. 1864 44

A novel assay for the determination of l-asparaginase activity in human plasma is described that is based on the HPLC quantitation of l-aspartic acid produced during enzyme incubation. Methods for monitoring l-asparagine depletion are also described. Chromatography of l-aspartic acid, l-asparagine and l-homoserine (the internal standard) involved derivatization with o-pthaldialdehyde, then separation from other amino acids on a Phenomenex Luna C(18) column using a 1 mL/min flow rate and a mobile phase consisting of di-potassium hydrogen orthophosphate propionate buffer, pH 6, with 10% methanol and 10% acetonitrile. Fluoresence detection was at excitation/emission wavelengths of 357/455 nm. Under these conditions l-aspartic acid, l-asparagine and l-homoserine had retention times of 3.5, 9.8 and 17.7 min, respectively. The l-asparaginase assay was linear from 0.1 to 10 U/mL activity and interday precision and accuracy were less than 13%. The limit of quantitation was approximately 0.03 U/mL. The assay utility was established in 12 children who received E. coli l-asparaginase as treatment for acute lymphoblastic leukaemia.
...
PMID:An isocratic fluorescence HPLC assay for the monitoring of l-asparaginase activity and l-asparagine depletion in children receiving E. colil-asparaginase for the treatment of acute lymphoblastic leukaemia. 1882 71

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.
...
PMID:Use of L-asparaginase in acute lymphoblastic leukemia: recommendations of the Polish Adult Leukemia Group. 1914 May 71

L-asparaginase (EC 3.5.1.1, L-ASNase) catalyses the hydrolysis of l-Asn, producing L-Asp and ammonia. This enzyme is an anti-neoplastic agent; it is used extensively in the chemotherapy of acute lymphoblastic leukaemia. In this study, we describe the use of in vitro directed evolution to create a new enzyme variant with improved thermal stability. A library of enzyme variants was created by a staggered extension process using the genes that code for the L-ASNases from Erwinia chrysanthemi and Erwinia carotovora. The amino acid sequences of the parental L-ASNases show 77% identity, but their half-inactivation temperature (T(m)) differs by 10 degrees C. A thermostable variant of the E. chrysamthemi enzyme was identified that contained a single point mutation (Asp133Val). The T(m) of this variant was 55.8 degrees C, whereas the wild-type enzyme has a T(m) of 46.4 degrees C. At 50 degrees C, the half-life values for the wild-type and mutant enzymes were 2.7 and 159.7 h, respectively. Analysis of the electrostatic potential of the wild-type enzyme showed that Asp133 is located at a neutral region on the enzyme surface and makes a significant and unfavourable electrostatic contribution to overall stability. Site-saturation mutagenesis at position 133 was used to further analyse the contribution of this position on thermostability. Screening of a library of random Asp133 mutants confirmed that this position is indeed involved in thermostability and showed that the Asp133Leu mutation confers optimal thermostability.
...
PMID:Engineering thermal stability of L-asparaginase by in vitro directed evolution. 1922 Aug 55

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%.
...
PMID:Evaluating the potential for enzymatic acrylamide mitigation in a range of food products using an asparaginase from Aspergillus oryzae. 1938 39

Patients with acute lymphoblastic leukemia (ALL), who develop antiasparaginase antibodies without clinical allergic reactions ("silent inactivation") during L: -asparaginase (L: -Asp) treatment, have poor outcomes. Ammonia is produced by hydrolysis of asparagine by L: -Asp. We postulated that plasma ammonia level might reflect the biological activity of L: -Asp. Five children with ALL treated according to the Tokyo Children's Cancer Study Group (TCCSG) protocol were enrolled. Plasma ammonia levels were analyzed immediately and 1 h after incubation at room temperature and "ex vivo ammonia production" was defined as increase in ammonia concentration. Ex vivo ammonia production well correlated with L: -Asp activity (r = 0.882, P < 0.01, n = 23). It always exceeded 170 microg/dL (170-345 microg/dL) in induction therapy. We found 3 patients whose ammonia production was negligible during later phases of therapy. Antiasparaginase antibody was detected and L: -Asp activity decreased in these patients. Ex vivo ammonia production is a surrogate marker of L: -Asp biological activity.
...
PMID:The ex vivo production of ammonia predicts L-asparaginase biological activity in children with acute lymphoblastic leukemia. 1976 19

A 66-year-old Japanese woman was referred to us because of severe anemia and fever and presented at our hospital. She was eventually diagnosed as having acute myeloblastic leukemia (AML; M0) with non-Hodgkin lymphoma (NHL). We investigated the therapeutic efficacy of L-asparaginase (L-Asp), vincristine and prednisolone for both her AML and NHL. Asparagine synthetase (AS) activity in her AML blast cells was undetectable. A lymph node biopsy specimen revealed NHL of the marginal zone B cell type. Complete remission (CR) of AML and NHL was achieved. CR of the AML lasted for 18 months without further consolidation therapy. We conclude that L-Asp can be an effective drug for the treatment of AML in which blasts are negative for AS.
...
PMID:Effect of L-asparaginase combined with vincristine and prednisolone on acute myeloblastic leukemia (M0) associated with non-Hodgkin lymphoma. 1981 10

A dough resembling traditional Spanish rosquillas was used as a model to represent classical fried-dough pastry to investigate the effects of asparaginase and heat treatment on amino acid levels and acrylamide mitigation. Wheat-based dough was deep fried at 180 and 200 degrees C for 4, 6, and 8 min. Two recipes were formulated by addition of different asparaginase levels (100 and 500 U/kg flour) to the dough. The temperature/time profile of the frying process, moisture, sugars, amino acids, acrylamide, and some indicators of the Maillard reaction (hydroxymethylfurfural, color, free fluorescence compounds, and browning) were determined to investigate the extent of the reaction and the effect on reactants. At the both levels of asparaginase used, 96-97% of the asparagine present was converted to aspartic acid, and consequently the acrylamide level was very efficiently reduced (up to 90%). The asparaginase also affected the content of glutamine and glutamic acid in dough, resulting in a 37% increase in glutamic acid compared with the untreated sample. Concerning color, browning and Maillard reaction parameters, no significant changes between untreated and enzymatically treated samples were observed, pointing out the potential industrial and domestic enzyme application.
...
PMID:Effect of L-asparaginase on acrylamide mitigation in a fried-dough pastry model. 1982 15

Asparaginase is an enzyme that breaks down extracellular asparagine into aspartic acid and ammonia. Depletion of extracellular asparagine inhibits the growth of lymphocytic leukemic cells. Unlike normal cells, lymphoblasts lack the enzyme to synthesize asparagine and therefore rely on an exogenous source of this amino acid to maintain cellular protein synthesis. Asparagine depletion results in nutritional deprivation, inhibition of protein synthesis, and subsequent apoptotic cell death in lymphoblasts. Asparaginase therapy is an essential component of the treatment protocol for acute lymphoblastic leukemia. The effect of asparaginase on protein synthesis may result in a number of toxicities, including thrombosis, pancreatitis, hyperglycemia, and hepatotoxicity. This review discusses the incidence of asparaginase-related adverse events, compares available asparaginase formulations with respect to the emergence of certain toxicities, and considers management strategies for these toxicities in patients with acute lymphoblastic leukemia.
...
PMID:Incidence and management of asparaginase-associated adverse events in patients with acute lymphoblastic leukemia. 2002 Jun 72


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>

---