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 Y
ATC code	L01XX02
DrugBank	BTD00011
UNII	G4FQ3CKY5R Y
KEGG	D02997 Y
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]

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

• Eukaryotic Linear Motif resource motif class CLV_TASPASE1
• MeSH Asparaginase
• Crisantaspase information from Macmillan Cancer Support
• [1] THE PET PHARMACY By Wendy C. Brooks, DVM, DipABVP; Educational Director, VeterinaryPartner.com
• U.S. NLM, NIH Drug Information Portal - Asparaginase

This antineoplastic or immunomodulatory drug article is a stub. You can help Wikipedia by expanding it.v · Categories: EC 3.5.1 Antineoplastic drugs Antineoplastic and immunomodulating drug stubs Wikimedia Foundation. 2010. Игры ⚽ Нужна курсовая? Wong Chuk Hang Sun Goes Down Look at other dictionaries: Asparaginase — (Homo sapiens) Masse/Länge Primärstruktur 309 Aminosäuren …   Deutsch Wikipedia asparaginase — ● asparaginase nom féminin Enzyme protéolytique utilisée en thérapeutique anticancéreuse (leucémies), détruisant la l asparagine, substance indispensable au développement de certaines cellules cancéreuses. asparaginase [aspaʀaʒinaz] n. f. ÉTYM.… …   Encyclopédie Universelle Asparaginase — As|pa|ra|gi|na|se [↑ ase], die; : ↑ Asparagin. * * * Asparaginase,   die, / n, in tierischen und pflanzlichen Geweben weitverbreitetes Enzym aus der Gruppe der Hydrolasen, das Asparagin zu Asparaginsäure und Ammoniak hy …   Universal-Lexikon asparaginase — Enzyme (EC 3.5.1.1) that hydrolyzes L asparagine to L aspartate and ammonia that is used as an anti tumour agent especially against lymphosarcoma and lymphatic leukaemia …   Dictionary of molecular biology asparaginase — /euh spar euh jeuh nays , nayz /, n. Biochem., Pharm. an enzyme that catalyzes the conversion of asparagine to aspartic acid and ammonia, used in the treatment of acute lymphocytic leukemia. [1960 65; ASPARAGINE + ASE] * * * …   Universalium asparaginase — noun An enzyme that catalyzes the hydrolysis of asparagine to aspartic acid, used in chemotherapy …   Wiktionary asparaginase — 1. An enzyme catalyzing the hydrolysis of l asparagine to l aspartic acid and ammonia. 2. The enzyme from Escherichia coli, used in the treatment of acute leukemia and other neoplastic diseases. Erwinia L a. L a. from Erwinia bacteria, used in… …   Medical dictionary Asparaginase — As|pa|ra|gi|na|se die; , n <zu ↑...ase> in tierischen u. pflanzlichen Geweben verbreitetes Enzym aus der Gruppe der ↑Hydrolasen, das ↑Asparagin spaltet (verwendet zur Therapie einiger Formen der Leukämie) …   Das große Fremdwörterbuch asparaginase — as·pa·rag·i·nase …   English syllables asparaginase — n. an enzyme that inhibits the growth of certain tumours. Crisantaspase, the form produced by the bacterium Erwinia chrysanthemi, is used in the treatment of acute lymphoblastic leukaemia. Administered by injection, it may cause allergic… …   The new mediacal dictionary 18+ © Academic, 2000-2024 Contact us: Technical Support, Advertising Dictionaries export, created on PHP, Joomla, Drupal, WordPress, MODx. Mark and share Search through all dictionaries Translate… Search Internet Share the article and excerpts Direct link … Do a right-click on the link above and select “Copy Link”