Asparaginase


Asparaginase
Asparaginase
Systematic (IUPAC) name
E. coli L-asparagine amidohydrolase
Clinical data
Trade names Elspar
AHFS/Drugs.com monograph
MedlinePlus a682046
Pregnancy cat. C(US)
Legal status POM (UK)
Pharmacokinetic data
Half-life 8-30 hrs
Identifiers
CAS number 9015-68-3 YesY
ATC code L01XX02
DrugBank BTD00011
UNII G4FQ3CKY5R YesY
KEGG D02997 YesY
Chemical data
Formula C1377H2208N382O442S17 
Mol. mass 31731.9 g/mol
 N(what is this?)  (verify)

Asparaginase (EC 3.5.1.1) 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[1]. 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)[2] and is also used in some mast cell tumor protocols. [3] 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.[2]

Contents

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[1].

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[4].

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.[2] 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.

References

  1. ^ 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.
  2. ^ 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. 
  3. ^ 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. 
  4. ^ 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. 

External links