Asparaginase Systematic (IUPAC) name E. coli L-asparagine amidohydrolase Clinical data Trade names Elspar AHFS/Drugs.com MedlinePlus Pregnancy cat. C(US) Legal status POM (UK) Pharmacokinetic data Half-life 8-30 hrs Identifiers CAS number ATC code L01 DrugBank UNII KEGG Chemical data Formula C1377H2208N382O442S17 Mol. mass 31731.9 g/mol (what is this?)
Asparaginase (EC 188.8.131.52) is an enzyme that catalyzes the hydrolysis of asparagine to aspartic acid. Asparaginases are naturally occurring enzymes expressed and produced by microorganisms. Different types of asparaginases can be used for different industrial and pharmaceutical purposes. The most common use of asparaginases is as a processing aid in the manufacture of food. Marketed under the brand names Acrylaway and PreventASe, asparaginases are used to reduce the formation of acrylamide, a suspected carcinogen, in starchy food products such as snacks and biscuits.
A different asparaginase is marketed as a drug under the brand name Elspar for the treatment of acute lymphoblastic leukemia (ALL) and is also used in some mast cell tumor protocols.  Unlike other chemotherapy agents, it can be given as an intramuscular, subcutaneous, or intravenous injection without fear of tissue irritation.
It is usually derived from Escherichia coli. Asparaginase produced by Erwinia chrysanthemi instead is known as crisantaspase (BAN), and is available in the United Kingdom under the trade name Erwinase.
Mechanism of action as a food processing aid
Aspariginase can be used as a food processing aid to reduce the formation of acrylamide, a suspected carcinogen, in starchy food products. Acrylamide is a chemical compound that is formed in starchy foods when they are baked or fried. During heating the amino acid asparagine, naturally present in starchy foods, is converted into acrylamide in a process called the Maillard reaction. The reaction is responsible for giving baked or fried foods their brown color, crust and toasted flavor.
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.
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.
Mechanism of action as a drug
The rationale behind asparaginase is that it takes advantage of the fact that ALL leukemic 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. 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.
Side effects in drug use
The main side effect is an allergic or hypersensitivity reaction; anaphylaxis is a possibility. Asparaginase has also been associated with pancreatitis. Additionally, it can also be associated with a coagulopathy as it decreases protein synthesis, including synthesis of coagulation factors (eg 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.
- ^ a b Kornbrust, B.A., Stringer, M.A., Lange, N.K. and Hendriksen, H.V. (2010) Asparaginase – an enzyme for acrylamide reduction in food products. In: Enzymes in Food Technology, 2nd Edition. (eds Robert J. Whitehurst and Maarten Van Oort). Wiley-Blackwell, UK, pp. 59-87.
- ^ a b c "8.1.5: Other antineoplastic drugs". British National Formulary (BNF 57). United Kingdom: BMJ Group and RPS Publishing. March 2009. p. 476. ISBN 9780853698456.
- ^ Appel IM, van Kessel-Bakvis C, Stigter R, Pieters R (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.
- ^ Hendriksen, H.V.; Kornbrust, B.A.; Oestergaard, P.R.; Stringer, M.A. (April 23, 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): 4168–4176. doi:10.1021/jf900174q. PMID 19388639. http://pubs.acs.org/doi/abs/10.1021/jf900174q. Retrieved October 8, 2010.
- Eukaryotic Linear Motif resource motif class CLV_TASPASE1
- MeSH Asparaginase
- Crisantaspase information from Macmillan Cancer Support
-  THE PET PHARMACY By Wendy C. Brooks, DVM, DipABVP; Educational Director, VeterinaryPartner.com
- U.S. NLM, NIH Drug Information Portal - Asparaginase
Intracellular chemotherapeutic agents/antineoplastic agents (L01) SPs/MIs
(M phase)Block microtubule assemblyBlock microtubule disassembly
inhibitorIIICrosslinking of DNA
(CCNS)Aziridines: Carboquone • ThioTEPA • Triaziquone • Triethylenemelamine
Photosensitizers/PDT OtherOther/ungroupedAmsacrine • Trabectedin • retinoids (Alitretinoin, Tretinoin) • Arsenic trioxide • asparagine depleters (Asparaginase/Pegaspargase) • Celecoxib • Demecolcine • Elesclomol • Elsamitrucin • Etoglucid • Lonidamine • HAMLET (human alpha-lactalbumin made lethal to tumor cells) • Lucanthone • Mitoguazone • Mitotane • Oblimersen • Omacetaxine mepesuccinate • mTOR inhibitors (Everolimus, Temsirolimus)
tumr, epon, para
Hydrolases: carbon-nitrogen non-peptide (EC 3.5) 3.5.1: Linear amides /
3.5.2: Cyclic amides/
3.5.3: Linear amidines/
3.5.4: Cyclic amidines/
3.5.99: Other Metabolism: amino acid metabolism · synthesis and catabolism enzymes (essential in CAPS) K→acetyl-CoA(see below) GG→pyruvate
This antineoplastic or immunomodulatory drug article is a stub. You can help Wikipedia by expanding it.