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Clinical data
Trade namesElspar, Spectrila, others
Other namescrisantaspase, colaspase
License data
  • AU: D
Routes of
Intramuscular (IM), intravenous (IV)
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • CA: ℞-only
  • UK: POM (Prescription only)
  • US: ℞-only
  • EU: Rx-only
  • In general: ℞ (Prescription only)
Pharmacokinetic data
Elimination half-life39-49 hours (IM), 8-30 hours (IV)
  • E. coli L-asparagine amidohydrolase
CAS Number
  • none
CompTox Dashboard (EPA)
ECHA InfoCard100.029.774 Edit this at Wikidata
Chemical and physical data
Molar mass31732.06 g·mol−1
 ☒NcheckY (what is this?)  (verify)

Asparaginase is an enzyme that is used as a medication and in food manufacturing.[1][2] As a medication, L-asparaginase is used to treat acute lymphoblastic leukemia (ALL).[1] It is given by injection into a vein, muscle, or under the skin.[1] A pegylated version is also available.[3] In food manufacturing it is used to decrease acrylamide.[2]

Common side effects when used by injection include allergic reactions, pancreatitis, blood clotting problems, high blood sugar, kidney problems, and liver dysfunction.[1] Use in pregnancy may harm the baby.[4] As a food it is generally recognized as safe.[2] Asparaginase works by breaking down the amino acid known as asparagine without which the cancer cells cannot make protein.[1]

Asparaginase was approved for medical use in the United States in 1978.[3] It is on the World Health Organization's List of Essential Medicines.[5] It is often made from Escherichia coli or Erwinia chrysanthemi.[3][6]


Asparaginases can be used for different industrial and pharmaceutical purposes.


E. coli strains are the main source of medical asparaginase.[7] Branded formulations (with different chemical and pharmacological properties) available in 1998 include Asparaginase Medac, Ciderolase, and Oncaspar.[7]:5 (Crasnitin has been discontinued.) Spectrila is a new recombinant E. coli asparaginase.[8]

Asparaginase produced by Dickeya dadantii (formerly called Erwinia chrysanthemi) instead is known as crisantaspase (BAN), and is available in the United Kingdom under the trade name Erwinase.[9]

One of the E. coli asparaginases marketed under the brand name Elspar for the treatment of acute lymphoblastic leukemia (ALL)[9] is also used in some mast cell tumor protocols.[10]

Unlike most of other chemotherapy agents, asparaginase can be given as an intramuscular, subcutaneous, or intravenous injection without fear of tissue irritation.

Food manufacturing[edit]

The most common use of asparaginases is as a processing aid in the manufacture of food. Asparaginases are used as a food processing aid to reduce the formation of acrylamide, a suspected carcinogen, in starchy food products such as snacks, biscuits and fried potato.[11][12] Asparaginases are marketed under the brand names Acrylaway and PreventASe.

Side effects[edit]

The main side effect is an allergic or hypersensitivity reaction; anaphylaxis is a possibility.[9] Additionally, it can also be associated with a coagulopathy as it decreases protein synthesis, including synthesis of coagulation factors (e.g. progressive isolated decrease of fibrinogen) and anticoagulant factor (generally antithrombin III; sometimes protein C & S as well), leading to bleeding or thrombotic events such as stroke.[7] Bone marrow suppression is common but only mild to moderate, rarely reaches clinical significance and therapeutic consequences are rarely required.[13]

Other common side effects include pancreatitis. These side effects mainly attributes to the dual activity of L.Asparaginase as it can also hydrolysis L.Glutamine to Glutamic acid and ammonia

Mechanism of action[edit]

As a food processing aid[edit]

Acrylamide is often formed in the cooking of starchy foods. During heating the amino acid asparagine, naturally present in starchy foods, undergoes a process called the Maillard reaction, which is responsible for giving baked or fried foods their brown color, crust, and toasted flavor. Suspected carcinogens such as acrylamide and some heterocyclic amines are also generated in the Maillard reaction. By adding asparaginase before baking or frying the food, asparagine is converted into another common amino acid, aspartic acid, and ammonium. As a result, asparagine cannot take part in the Maillard reaction, and therefore the formation of acrylamide is significantly reduced. Complete acrylamide removal is probably not possible due to other, minor asparagine-independent formation pathways.[11]

As a food processing aid, asparaginases can effectively reduce the level of acrylamide up to 90% in a range of starchy foods without changing the taste and appearance of the end product.[14][12]

As a drug[edit]

The rationale behind asparaginase is that it takes advantage of the fact that acute lymphoblastic leukemia cells and some other suspected tumor cells are unable to synthesize the non-essential amino acid asparagine, whereas normal cells are able to make their own asparagine; thus leukemic cells require high amount of asparagine.[15] These leukemic cells depend on circulating asparagine. Asparaginase, however, catalyzes the conversion of L-asparagine to aspartic acid and ammonia. This deprives the leukemic cell of circulating asparagine, which leads to cell death.[16]

Enzyme regulation[edit]

Type I L-asparaginase protein may use the morpheein model of allosteric regulation.[17]


Normal asparaginase costs less than its pegylated version, pegaspargase.[18] However, because it doesn't stay as long in the body, the injections need to be more frequent, with the result that total cost of treatment may be lower for the pegylated version.[18]


The discovery and development of asparaginase as an anti-cancer drug began in 1953, when scientists first observed that lymphomas in rat and mice regressed after treatment with guinea pig serum.[19] Later it was found out that it is not the serum itself which provoke the tumour regression, but rather the enzyme asparaginase.[20]

After researchers comparing different kinds of asparaginases, the one derived from Escherichia coli and Erwinia chrysanthemi turned out to have the best anti-cancer ability. E. coli has thereby become the main source of asparaginase due to the factor that it is also easy to produce in large amount.[7]


Crisantaspase is British Approved Name (BAN) for asparaginase obtained from Erwinia chrysanthemi. Colaspase is the BAN of asparaginase obtained from Escherichia coli.[21][7][9] The United States Adopted Name of crisantaspase is asparaginase Erwinia chrysanthemi.[21] Elspar, Kidrolase, Leunase and Spectrila are brand names for colaspase, while Erwinase and Erwinaze are brand names for crisantaspase.[21] The pegylated version of colaspase is called pegaspargase. Oncaspar is the brand name of pegaspargase.[21]


  1. ^ a b c d e "Asparaginase". The American Society of Health-System Pharmacists. Archived from the original on 27 March 2017. Retrieved 8 December 2016.
  2. ^ a b c Gökmen V (2015). Acrylamide in Food: Analysis, Content and Potential Health Effects. Academic Press. p. 415. ISBN 9780128028759. Archived from the original on 2016-12-21.
  3. ^ a b c Kim K, Roh JK, Wee H, Kim C (2016). Cancer Drug Discovery: Science and History. Springer. p. 147. ISBN 9789402408447. Archived from the original on 2016-12-21.
  4. ^ "Asparaginase escherichia coli (Elspar) Use During Pregnancy". Archived from the original on 27 March 2017. Retrieved 20 December 2016.
  5. ^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  6. ^ Farmer PB, Walker JM (2012). The Molecular Basis of Cancer. Springer Science & Business Media. p. 279. ISBN 9781468473131. Archived from the original on 2016-12-21.
  7. ^ a b c d e Avramis VI, Sencer S, Periclou AP, Sather H, Bostrom BC, Cohen LJ, et al. (March 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): 1986–94. doi:10.1016/S1040-8428(98)00015-8. PMID 11877270.
  8. ^ "Spectrila 10,000 U powder for concentrate for solution for infusion - Summary of Product Characteristics (SmPC) - (eMC)". Archived from the original on 2016-11-09. Retrieved 2016-11-08.
  9. ^ a b c d "8.1.5: Other antineoplastic drugs". British National Formulary (BNF 57). United Kingdom: BMJ Group and RPS Publishing. March 2009. p. 476. ISBN 978-0-85369-845-6.
  10. ^ Appel IM, van Kessel-Bakvis C, Stigter R, Pieters R (November 2007). "Influence of two different regimens of concomitant treatment with asparaginase and dexamethasone on hemostasis in childhood acute lymphoblastic leukemia". Leukemia. 21 (11): 2377–80. doi:10.1038/sj.leu.2404793. PMID 17554375.
  11. ^ a b Kornbrust BA, Stringer MA, Lange NE, Hendriksen HV, Whitehurst R, Oort MV (2010). "Enzymes in food technology.". In Whitehurst RJ, Van Oort M (eds.). Asparaginase–an enzyme for acrylamide reduction in food products. 2. UK: Wiley-Blackwell. pp. 59–87.
  12. ^ a b Farahat MG, Amr D, Galal A (January 2020). "Molecular cloning, structural modeling and characterization of a novel glutaminase-free L-asparaginase from Cobetia amphilecti AMI6". International Journal of Biological Macromolecules. 143: 685–695. doi:10.1016/j.ijbiomac.2019.10.258. PMID 31759010.
  13. ^ Johnston PG, Hardisty RM, Kay HE, Smith PG (July 1974). "Myelosuppressive effect of colaspase (L-asparaginase) in initial treatment of acute lymphoblastic leukaemia". British Medical Journal. 3 (5923): 81–3. doi:10.1136/bmj.3.5923.81. PMC 1611087. PMID 4604804.
  14. ^ Hendriksen HV, Kornbrust BA, Østergaard PR, Stringer MA (May 2009). "Evaluating the potential for enzymatic acrylamide mitigation in a range of food products using an asparaginase from Aspergillus oryzae". Journal of Agricultural and Food Chemistry. 57 (10): 4168–76. doi:10.1021/jf900174q. PMID 19388639.
  15. ^ Fernandes HS, Silva Teixeira CS, Fernandes PA, Ramos MJ, Cerqueira NM (March 2017). "Amino acid deprivation using enzymes as a targeted therapy for cancer and viral infections". Expert Opinion on Therapeutic Patents. 27 (3): 283–297. doi:10.1080/13543776.2017.1254194. PMID 27813440. S2CID 7768944.
  16. ^ Broome JD (1981). "L-Asparaginase: discovery and development as a tumor-inhibitory agent". Cancer Treatment Reports. 65 Suppl 4: 111–4. PMID 7049374.
  17. ^ Selwood T, Jaffe EK (March 2012). "Dynamic dissociating homo-oligomers and the control of protein function". Archives of Biochemistry and Biophysics. 519 (2): 131–43. doi:10.1016/ PMC 3298769. PMID 22182754.
  18. ^ a b Gad, Shayne Cox (2007-05-25). Handbook of Pharmaceutical Biotechnology. John Wiley & Sons. p. 730. ISBN 978-0-470-11710-1.
  19. ^ Kidd JG (December 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". The Journal of Experimental Medicine. 98 (6): 565–82. doi:10.1084/jem.98.6.565. PMC 2136344. PMID 13109110.
  20. ^ Broome JD (July 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". The Journal of Experimental Medicine. 118 (1): 99–120. doi:10.1084/jem.118.1.99. PMC 2137570. PMID 14015821.
  21. ^ a b c d Brayfield, A, ed. (June 2017). "Asparaginase: Martindale: The Complete Drug Reference". MedicinesComplete. London, UK: Pharmaceutical Press. Retrieved 9 August 2017.

External links[edit]