What makes a good new therapeutic l-asparaginase?

• Aghaiypour K, Wlodawer A, Lubkowski J (2001) Structural basis for the activity and substrate specificity of Erwinia chrysanthemi L-asparaginase. Biochemistry 40(19):5655–5664

  CAS  PubMed  Google Scholar 

• Albertsen BK et al (2001) Monitoring of Erwinia asparaginase therapy in childhood ALL in the Nordic countries. Br J Clin Pharmacol 52(4):433–437

  CAS  PubMed  PubMed Central  Google Scholar 

• Alrumman SA et al (2019) Production and anticancer activity of an L-asparaginase from Bacillus licheniformis isolated from the Red Sea, Saudi Arabia. Sci Rep 9(1):3756

  CAS  PubMed  PubMed Central  Google Scholar 

• Andrulis IL, Argonza R, Cairney AEL (1990) Molecular and genetic characterization of human cell lines resistant to L-asparaginase and albizziin. Somatic Cell Mol Genet 16(1):59–65

  CAS  Google Scholar 

• Angiolillo AL et al (2014) Pharmacokinetic and pharmacodynamic properties of calaspargase pegol Escherichia coli L-asparaginase in the treatment of patients with acute lymphoblastic leukemia: results from children’s oncology group study AALL07P4. J Clin Oncol 32(34):3874–3882

  CAS  PubMed  PubMed Central  Google Scholar 

• Appel IM et al (2008) Pharmacokinetic, pharmacodynamic and intracellular effects of PEG-asparaginase in newly diagnosed childhood acute lymphoblastic leukemia: results from a single agent window study. Leukemia 22(9):1665–1679. https://doi.org/10.1038/leu.2008.165

  Article  CAS  PubMed  Google Scholar 

• Armstrong JK et al (2007) Antibody against poly(ethylene glycol) adversely affects PEG-asparaginase therapy in acute lymphoblastic leukemia patients. Cancer 110(1):103–111

  PubMed  Google Scholar 

• Ashok A et al (2019) Microbes producing L-asparaginase free of glutaminase and urease isolated from extreme locations of antarctic soil and moss. Sci Rep 9(1):1423

  PubMed  PubMed Central  Google Scholar 

• Asselin BL (1999) The three asparaginases comparative pharmacology and optimal use in childhood leukemia. Adv Exp Med Biol 457:621–629

  CAS  PubMed  Google Scholar 

• Avramis VI et al (2002) A randomized comparison of native Escherichia coli asparaginase and polyethylene glycol conjugated asparaginase for treatment of children with newly diagnosed standard-risk acute lymphoblastic leukemia: a Children’s Cancer Group study. Blood 99(6):1986–1994

  CAS  PubMed  Google Scholar 

• Bachet J-B et al (2015) Asparagine synthetase expression and phase I study with L-asparaginase encapsulated in red blood cells in patients with pancreatic adenocarcinoma. Pancreas 44(7):1141–1147. https://doi.org/10.1097/MPA.0000000000000394

  Article  CAS  PubMed  Google Scholar 

• Belén LH et al (2019) A structural in silico analysis of the immunogenicity of L-asparaginase from Escherichia coli and Erwinia carotovora. Biologicals 59:47–55

  PubMed  Google Scholar 

• Boos J et al (1996) Monitoring of asparaginase activity and asparagine levels in children on different asparaginase preparations. Eur J Cancer A 32(9):1544–1550

  Google Scholar 

• Broome J (1963) Evidence that the L-asparaginase of guinea pig serum is responsible for its antilymphoma effects. I. Properties of the L-asparaginase of guinea pig serum in relation to those of the antilymphoma substance. J Exp Med 118(1):99–120

  CAS  PubMed  PubMed Central  Google Scholar 

• Cetinbas F, Yelken B, Gulbas Z (2010) Role of glutamine administration on cellular immunity after total parenteral nutrition enriched with glutamine in patients with systemic inflammatory response syndrome. J Crit Care 25(4):661. (e1-661.e6)

  PubMed  Google Scholar 

• Cha YH et al (2015) Catabolic metabolism during cancer EMT. Arch Pharm Res 38(3):313–320

  CAS  PubMed  Google Scholar 

• Chan WK et al (2014) The glutaminase activity of L-asparaginase is not required for anticancer activity against ASNS-negative cells. Blood 123(23):3596–3607

  CAS  PubMed  PubMed Central  Google Scholar 

• Chohan SM et al (2018) Pcal_0970: an extremely thermostable L-asparaginase from Pyrobaculum calidifontis with no detectable glutaminase activity. Folia Microbiol 64(3):313–320

  Google Scholar 

• Committee for Medicinal Products for Human Use (2018) Withdrawal Assessment Report GRASPA. London.

• Cooney DA, Capizzi RL, Handschumacher RE (1970) Evaluation of L-asparagine metabolism in animals and man. Cancer Res 30(4):929–935

  CAS  PubMed  Google Scholar 

• Darvishi F, Faraji N, Shamsi F (2019) Production and structural modeling of a novel asparaginase in Yarrowia lipolytica. Int J Biol Macromol 125:955–961

  CAS  PubMed  Google Scholar 

• de Brito AEM et al (2019) Poly (lactic-co-glycolic acid) nanospheres allow for high l-asparaginase encapsulation yield and activity. Mater Sci Eng C 98:524–534

  Google Scholar 

• DeBerardinis RJ et al (2007) Beyond aerobic glycolysis: Transformed cells can engage in glutamine metabolism that exceeds the requirement for protein and nucleotide synthesis. Proc Natl Acad Sci 104(49):19345–19350

  CAS  PubMed  PubMed Central  Google Scholar 

• Derst C, Henseling J, Röhm K-H (2000) Engineering the substrate specificity of Escherichia coli asparaginase II. Selective reduction of glutaminase activity by amino acid replacements at position 248. Protein Sci 9(10):2009–2017

  CAS  PubMed  PubMed Central  Google Scholar 

• Deshpande N, Choubey P, Agashe M (2014) Studies on optimization of growth parameters for l-asparaginase production by Streptomyces ginsengisoli. Sci World J 2014:1–6

  Google Scholar 

• Dinndorf PA et al (2007) FDA drug approval summary: pegaspargase (Oncaspar(R)) for the first-line treatment of children with acute lymphoblastic leukemia (ALL). The Oncologist 12(8):991–998

  CAS  PubMed  Google Scholar 

• Dübbers A et al (2000) Asparagine synthetase activity in paediatric acute leukaemias: AML-M5 subtype shows lowest activity. Br J Haematol 109(2):427–429

  PubMed  Google Scholar 

• Duval M et al (2002) Comparison of Escherichia coli-asparaginase with Erwinia-asparaginase in the treatment of childhood lymphoid malignancies: results of a randomized European Organisation for Research and Treatment of cancer-children’s leukemia group phase 3 trial. Blood 99(8):2734–2739

  CAS  PubMed  Google Scholar 

• Eagle H et al (1956) The growth response of mammalian cells in tissue culture to L-glutamine and L-glutamic acid. J Biol Chem 218(2):607–616

  CAS  PubMed  Google Scholar 

• Ehrman M, Cedar H, Schwartz JH (1971) L-asparaginase II of Escherichia coli. Studies on the enzymatic mechanism of action. J Biol Chem 246(1):88–94.

  CAS  PubMed  Google Scholar 

• El-Naggar NE-A et al (2016) Purification, characterization, cytotoxicity and anticancer activities of L-asparaginase, anti-colon cancer protein, from the newly isolated alkaliphilic Streptomyces fradiae NEAE-82. Sci Rep 6(1):32926

  CAS  PubMed  PubMed Central  Google Scholar 

• Emadi A et al (2018) Asparaginase Erwinia chrysanthemi effectively depletes plasma glutamine in adult patients with relapsed/refractory acute myeloid leukemia. Cancer Chemother Pharmacol 81:217–222

  CAS  PubMed  Google Scholar 

• Feng Y et al (2019) Improvement of catalytic efficiency and thermal stability of l-asparaginase from Bacillus subtilis 168 through reducing the flexibility of the highly flexible loop at N-terminus. Process Biochem 78:42–49

  CAS  Google Scholar 

• Fine BM et al (2005) A genome-wide view of the in vitro response to L-asparaginase in acute lymphoblastic leukemia. Cancer Res 65(1):291–299

  CAS  PubMed  Google Scholar 

• Gervais D, Foote N (2014) Recombinant deamidated mutants of Erwinia chrysanthemi L-asparaginase have similar or increased activity compared to wild-type enzyme. Mol Biotechnol 56(10):865–877

  CAS  PubMed  Google Scholar 

• Gervais D et al (2015) ‘Structural characterisation of non-deamidated acidic variants of erwinia chrysanthemi l-asparaginase using small-angle x-ray scattering and ion-mobility mass spectrometry. Pharm Res 32(11):3636–3648

  CAS  PubMed  Google Scholar 

• Gervais D et al (2017) Understanding the process-induced formation of minor conformational variants of Erwinia chrysanthemi l-asparaginase. Enzyme Microb Technol 98:26–33

  CAS  PubMed  Google Scholar 

• Goddard TD et al (2018) UCSF ChimeraX: Meeting modern challenges in visualization and analysis. Protein Sci 27(1):14–25

  CAS  PubMed  Google Scholar 

• Han Y et al (2016) Application of glutamine-enriched nutrition therapy in childhood acute lymphoblastic leukemia. Nutr J 15(1):65

  PubMed  PubMed Central  Google Scholar 

• Haskell CM et al (1969) L-asparaginase. New Engl J Med 281(19):1028–1034

  CAS  PubMed  Google Scholar 

• Hays JL et al (2013) A phase II clinical trial of polyethylene glycol-conjugated L-asparaginase in patients with advanced ovarian cancer: Early closure for safety. Mol Clin Oncol 1(3):565–569

  CAS  PubMed  PubMed Central  Google Scholar 

• Higashiguchi T et al (1993) Effect of glutamine on protein synthesis in isolated intestinal epithelial cells. J Parenter Enteral Nutr 17(4):307–314

  CAS  Google Scholar 

• Ho PP et al (1970) Crystalline L-asparaginase from Escherichia coli B.I. Purification and chemical characterization. J Biol Chem 254(14):3708–3715

  Google Scholar 

• Huang L et al (2014) ‘Biochemical characterization of a novel L-asparaginase with low glutaminase activity from Rhizomucor miehei and its application in food safety and leukemia treatment. Appl Environ Microbiol 80(5):1561–1569

  PubMed  PubMed Central  Google Scholar 

• Husain I et al (2016) Purification and characterization of glutaminase free asparaginase from enterobacter cloacae: Invitro evaluation of cytotoxic potential against human myeloid leukemia HL-60 cells. PLoS ONE 11(2):e0148877

  PubMed  PubMed Central  Google Scholar 

• Iida K et al (2007) PERK eIF2 alpha kinase is required to regulate the viability of the exocrine pancreas in mice. BMC Cell Biol 8(1):38

  PubMed  PubMed Central  Google Scholar 

• Kante RK et al (2018) Optimized upstream and downstream process conditions for the improved production of recombinant human asparaginase (rhASP) from Escherichia coli and its characterization. Biologicals 56:45–53

  CAS  PubMed  Google Scholar 

• Kidd JG (1953) Regression of transplanted lymphomas induced in vivo by means of normal guinea pig serum I. Course of transplanted cancers of various kinds in mice and rats given guinea pig serum, horse serum, or rabbit serum. J Exp Med 98(6):565–582

  CAS  PubMed  PubMed Central  Google Scholar 

• Kotzia GA, Labrou NE (2007) L-asparaginase from Erwinia Chrysanthemi 3937: cloning, expression and characterization. J Biotechnol 127(4):657–669

  CAS  PubMed  Google Scholar 

• Krall AS et al (2016) Asparagine promotes cancer cell proliferation through use as an amino acid exchange factor. Nat Commun 7(11457):1–13

  Google Scholar 

• Lambertucci AC et al (2012) Glutamine supplementation stimulates protein-synthetic and inhibits protein-degradative signaling pathways in skeletal muscle of diabetic rats. PLoS ONE 7(12):50390

  Google Scholar 

• Leslie M et al (2006) Expression levels of asparagine synthetase in blasts from children and adults with acute lymphoblastic leukaemia. Br J Haematol 132(6):740–742

  CAS  PubMed  Google Scholar 

• Li L-Z et al (2007) Enhancing the thermostability of Escherichia coli l-asparaginase II by substitution with pro in predicted hydrogen-bonded turn structures. Enzyme Microb Technol 41(4):523–527

  CAS  Google Scholar 

• Liao GY et al (2019) Blockage of glutamine-dependent anaplerosis affects mTORC1/2 activity and ultimately leads to cellular senescence-like response. Biol Open 8(5):bio038257

  PubMed  PubMed Central  Google Scholar 

• Liu C, Luo L, Lin Q (2019) Antitumor activity and ability to prevent acrylamide formation in fried foods of asparaginase from soybean root nodules. J Food Biochem 43(3):e12756

  PubMed  Google Scholar 

• Lubkowski J et al (2003) Atomic resolution structure of Erwinia chrysanthemi L-asparaginase. Acta crystallogr D Biol crystallogr 59(1):84–92

  PubMed  Google Scholar 

• Maggi M et al (2017) A protease-resistant Escherichia coli asparaginase with outstanding stability and enhanced anti-leukaemic activity in vitro. Sci Rep 7(1):14479

  PubMed  PubMed Central  Google Scholar 

• Marini BL et al (2017) Catalyzing improvements in ALL therapy with asparaginase. Blood Rev 31(5):328–338

  CAS  PubMed  Google Scholar 

• Meena B et al (2016) Molecular expression of l-asparaginase gene from Nocardiopsis alba NIOT-VKMA08 in Escherichia coli: a prospective recombinant enzyme for leukaemia chemotherapy. Gene 590(2):220–226

  CAS  PubMed  Google Scholar 

• Michaelis L et al (2011) The original michaelis constant: translation of the 1913 Michaelis-Menten paper. Biochemistry 50(39):8264–8269

  PubMed  Google Scholar 

• Miller M et al (1993) A left-handed crossover involved in amidohydrolase catalysis Crystal structure of Erwinia chrysanthemi L-asparaginase with bound L-aspartate. FEBS lett 328(3):275–279

  CAS  PubMed  Google Scholar 

• Moe-Byrne T, Brown JV, McGuire W (2016) Glutamine supplementation to prevent morbidity and mortality in preterm infants. In W. McGuire (ed.), Cochrane database of systematic reviews. (p. CD001457). Chichester:Wiley.

• Mohan Kumar NS, Manonmani HK (2013) Purification, characterization and kinetic properties of extracellular l-asparaginase produced by Cladosporium sp.. World J Microbiol Biotechnol 29(4):577–587

  CAS  PubMed  Google Scholar 

• Moola ZB et al (1994) Erwinia chrysanthemi L-asparaginase: epitope mapping and production of antigenically modified enzymes. Biochem J 302(Pt 3):921–927

  CAS  PubMed  PubMed Central  Google Scholar 

• Müller HJ et al (2000) Pegylated asparaginase (Oncaspar) in children with ALL: drug monitoring in reinduction according to the ALL/NHL-BFM 95 protocols. Br J Haematol 110(2):379–384

  PubMed  Google Scholar 

• Nguyen HA, Su Y, Lavie A (2016) Design and characterization of Erwinia Chrysanthemi l-Asparaginase variants with diminished l-glutaminase activity. J Biol Chem 291(34):17664–17676

  CAS  PubMed  PubMed Central  Google Scholar 

• Nguyen HA, Durden DL, Lavie A (2017) The differential ability of asparagine and glutamine in promoting the closed/active enzyme conformation rationalizes the Wolinella succinogenes L-asparaginase substrate specificity. Sci Rep 7:41643

  CAS  PubMed  PubMed Central  Google Scholar 

• Nguyen HA et al (2018) A novel L-asparaginase with low L-glutaminase coactivity is highly efficacious against both T- and B-cell acute lymphoblastic leukemias in vivo. Cancer Res 78(6):1549–1560

  CAS  PubMed  PubMed Central  Google Scholar 

• Oettgen HF et al. (1970) Toxicity of E. coli L-asparaginase in man. Cancer 25(2):253–278.

  CAS  PubMed  Google Scholar 

• Offman MN et al (2011) Rational engineering of L-asparaginase reveals importance of dual activity for cancer cell toxicity. Blood 117(5):1614–1621

  CAS  PubMed  Google Scholar 

• Ogawa C et al (2017) ‘Plasma asparaginase activity, asparagine concentration, and toxicity after administration of Erwinia asparaginase in children and young adults with acute lymphoblastic leukemia: Phase I/II clinical trial in Japan. Pediatr Blood Cancer 64(9):1–8

  Google Scholar 

• Ollenschläger G et al (1988) Asparaginase-induced derangements of glutamine metabolism: the pathogenetic basis for some drug-related side-effects. Eur J Clin Investig 18(5):512–516

  Google Scholar 

• Palmieri EM et al (2017) Blockade of glutamine synthetase enhances inflammatory response in microglial cells. Antioxid Redox Signal 26(8):351–363

  CAS  PubMed  PubMed Central  Google Scholar 

• Panosyan EH et al (2004) Deamination of glutamine is a prerequisite for optimal asparagine deamination by asparaginases in vivo (CCG-1961). Anticancer Res 24(2C):1121–1125

  CAS  PubMed  Google Scholar 

• Pant A, Cao S, Yang Z (2019) Asparagine is a critical limiting metabolite for vaccinia virus protein synthesis during glutamine deprivation. J Virol 93(13):1–17

  Google Scholar 

• Parimi PS et al (2002) Glutamine and leucine nitrogen kinetics and their relation to urea nitrogen in newborn infants. Am J Physiol Endocrinol Metab 282(3):E618–E625

  CAS  PubMed  Google Scholar 

• Parmentier JH et al (2015) Glutaminase activity determines cytotoxicity of L-asparaginases on most leukemia cell lines. Leukemia Res 39(7):757–762

  CAS  Google Scholar 

• Pinheiro JPV et al (1999) Pharmacokinetic dose adjustment of Erwinia asparaginase in protocol II of the paediatric ALL/NHL-BFM treatment protocols. Br J Haematol 104:313–320

  CAS  Google Scholar 

• Plourde PV et al (2014) Safety profile of asparaginase Erwinia chrysanthemi in a large compassionate-use trial. Pediatr Blood Cancer 61(7):1232–1238

  CAS  PubMed  Google Scholar 

• Pritsa AA, Kyriakidis DA (2001) L-asparaginase of thermus thermophilus: purification, properties and identificaation of essential amino acids for its catalytic activity. Mol Cell Biochem 216(1/2):93–101

  CAS  PubMed  Google Scholar 

• Purwaha P et al (2014) Targeted metabolomic analysis of amino acid response to L-asparaginase in adherent cells. Metabolomics 10(5):909–919

  CAS  PubMed  PubMed Central  Google Scholar 

• Radha R, Arumugam N, Gummadi SN (2018) Glutaminase free L-asparaginase from Vibrio cholerae: heterologous expression, purification and biochemical characterization. Int J Biol Macromol 111:129–138

  CAS  PubMed  Google Scholar 

• Ramya LN, Pulicherla KK (2015) Studies on deimmunization of antileukaemic L-asparaginase to have reduced clinical immunogenicity—an in silico approach. Pathol Oncol Res 21(4):909–920

  CAS  PubMed  Google Scholar 

• Ratnikov B et al (2015) Glutamate and asparagine cataplerosis underlie glutamine addiction in melanoma. Oncotarget 6(10):7379–7389

  PubMed  PubMed Central  Google Scholar 

• Rau RE et al (2018) Outcome of pediatric patients with acute lymphoblastic leukemia/lymphoblastic lymphoma with hypersensitivity to pegaspargase treated with PEGylated Erwinia asparaginase, pegcrisantaspase: a report from the children’s oncology Group. Pediatr Blood Cancer 65(3):1–14

  Google Scholar 

• Reinert RB et al (2006) Role of glutamine depletion in directing tissue-specific nutrient stress responses to L-asparaginase. J Biol Chem 281(42):31222–31233

  CAS  PubMed  Google Scholar 

• Riccardi R et al (1981) L-asparaginase pharmacokinetics and asparagine levels in cerebrospinal fluid of rhesus monkeys and humans. Cancer Res 11:4554–4558

  Google Scholar 

• Rigouin C et al (2017) Discovery of human-like L-asparaginases with potential clinical use by directed evolution. Sci Rep 7(1):10224

  PubMed  PubMed Central  Google Scholar 

• Roskoski R (2011) Michaelis-menten kinetics’, xPharm: the comprehensive pharmacology reference. Elsevier Inc., Amsterdam, pp 1–10

  Google Scholar 

• Salzer WL et al (2014) Development of asparaginase Erwinia chrysanthemi for the treatment of acute lymphoblastic leukemia. Ann New York Acad Sci 1329(1):81–92

  CAS  Google Scholar 

• Sands S et al (2017) Glutamine for the treatment of vincristine-induced neuropathy in children and adolescents with cancer. Support Care Cancer 25(3):701–708

  PubMed  Google Scholar 

• Sindhu R, Manonmani HK (2018) Expression and characterization of recombinant l-asparaginase from Pseudomonas fluorescens. Protein Exp Purif 143:83–91

  CAS  Google Scholar 

• Stark RM et al (1997) Amino acid utilisation and deamination of glutamine and asparagine by Helicobacter pylori. J Med Microbiol 46(9):793–800

  CAS  PubMed  Google Scholar 

• Sudhir AP et al (2016) Enhanced catalysis of l-asparaginase from Bacillus licheniformis by a rational redesign. Enzyme Microb Technol 86:1–6

  CAS  PubMed  Google Scholar 

• Swain AL et al (1993) Crystal structure of Escherichia coli L-asparaginase, an enzyme used in cancer therapy. Proc Natl Acad Sci USA 90(4):1474–1478

  CAS  PubMed  PubMed Central  Google Scholar 

• Tanaka Y et al (2016) Elemental diet plus glutamine for the prevention of mucositis in esophageal cancer patients receiving chemotherapy: a feasibility study. Support Care Cancer 24(2):933–941

  PubMed  Google Scholar 

• Tao K-M et al (2014) Glutamine supplementation for critically ill adults. Cochrane Database of Syst Rev 9:1–119

  CAS  Google Scholar 

• Torres-Obreque K et al (2019) Production of a novel N-terminal PEGylated crisantaspase. Biotechnol Appl Biochem 66(3):281–289

  CAS  PubMed  Google Scholar 

• Tsujimoto T et al (2015) L-glutamine decreases the severity of mucositis induced by chemoradiotherapy in patients with locally advanced head and neck cancer : a double-blind. randomized, placebo-controlled trial. Oncol Rep 33:33–39

  CAS  PubMed  Google Scholar 

• Vala AK et al (2018) Characterization of L-asparaginase from marine-derived Aspergillus niger AKV-MKBU, its antiproliferative activity and bench scale production using industrial waste. Int J Biol Macromol 108:41–46

  CAS  PubMed  Google Scholar 

• van der Sluis IM et al (2016) Consensus expert recommendations for identification and management of asparaginase hypersensitivity and silent inactivation. Haematologica 101(3):279–285

  PubMed  PubMed Central  Google Scholar 

• van Zaanen HCT et al (1994) Parenteral glutamine dipeptide supplementation does not ameliorate chemotherapy-induced toxicity. Cancer 74(10):2879–2884

  PubMed  Google Scholar 

• van Zanten ARH, Hofman Z, Heyland DK (2015) Consequences of the REDOXS and METAPLUS Trials. J Parenter Enteral Nutr 39(8):890–892

  Google Scholar 

• Vicentini GE et al (2016) Experimental cancer cachexia changes neuron numbers and peptide levels in the intestine: partial protective effects after dietary supplementation with L-glutamine. PLoS ONE 11(9):0162998

  Google Scholar 

• Vimal A, Kumar A (2017) In vitro screening and in silico validation revealed key microbes for higher production of significant therapeutic enzyme l-asparaginase. Enzyme and Microbial Technol 98:9–17

  CAS  Google Scholar 

• Vrooman LM et al (2016) Activity and toxicity of intravenous Erwinia asparaginase following allergy to E. Coli-derived asparaginase in children and adolescents with acute lymphoblastic leukemia. Pediatr Blood Cancer 63(2):228–233.

  Google Scholar 

• Wan S et al (2016) Chitosan-modified lipid nanovesicles for efficient systemic delivery of l-asparaginase. Colloids Surf B 143:278–284

  CAS  Google Scholar 

• Wang B et al (2003) Evaluation of immunologic crossreaction of antiasparaginase antibodies in acute lymphoblastic leukemia (ALL) and lymphoma patients. Leukemia 17(8):1583–1588

  CAS  PubMed  Google Scholar 

• Wang K et al (2017) Glutamine supplementation suppresses herpes simplex virus reactivation. J Clin Investig 127(7):2626–2630

  PubMed  PubMed Central  Google Scholar 

• Warrell RP et al (1980) Phase I evaluation of succinylated acinetobacter glutaminase-asparaginase in adults. Cancer Res 40(12):4546–4551

  PubMed  Google Scholar 

• Wernerman J (2015) How to understand the results of studies of glutamine supplementation. Crit Care 19:385

  PubMed  PubMed Central  Google Scholar 

• Wriston JC (1985) L-asparaginase: a review. Methods Enzymol 113:608–618

  CAS  PubMed  Google Scholar 

• Zalewska-Szewczyk B et al (2009) The cross-reactivity of anti-asparaginase antibodies against different l-asparaginase preparations. Clin Exp Med 9(2):113–116

  CAS  PubMed  Google Scholar 

• Zhang J et al (2014) Asparagine plays a critical role in regulating cellular adaptation to glutamine depletion. Mol Cell 56(2):205–218

  CAS  PubMed  PubMed Central  Google Scholar 

• Zhu Y et al (2017) A critical role of glutamine and asparagine γ-nitrogen in nucleotide biosynthesis in cancer cells hijacked by an oncogenic virus. mBio 8(4):e01179.

• Ziegler TR et al (2005) Parenteral glutamine increases serum heat shock protein 70 in critically ill patients. Intensive Care Med 31:1079–1086

  PubMed  Google Scholar 

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