asparaginase
American Heritage Dictionary:
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as·par·a·gin·ase
(ə-spăr'ə-jə-nās', -nāz') 
n.
An enzyme isolated from bacteria that catalyzes the hydrolysis of asparagine and is used in the chemotherapeutic treatment of leukemia.
n.
An enzyme isolated from bacteria that catalyzes the hydrolysis of asparagine and is used in the chemotherapeutic treatment of leukemia.
Gale Encyclopedia of Cancer:
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Asparaginase
Key Terms: Acute lymphocytic leukemia, Anaphylaxis.
Definition
Asparaginase (also known as L-asparaginase, and sold under the brand name Elspar) is a medicine used to stop growth of cancer and formation of new cancer cells.
Purpose
Asparaginase is used as part of an induction regimen for the treatment of acute lymphocytic leukemia (ALL) in children.
Description
Asparaginase is an enzyme made from the bacteria escherichia coli (E. coli). In this country, two forms of asparaginase are available: one made from E. coli, and a slightly changed version of the E.Coli form linked to polyethylene glycol (PEG) molecule. This PEG-linked asparaginase is called pegaspargase. This version was made available in 1994, is more expensive than the other form, and is mainly used in patients who have developed an allergy to E. Coli. Another natural form of asparaginase made from the plant bacteria erwinia carotovora is known by the brand name Erwinar and can be specially obtained for patients who develop a severe allergy to E. coli asparaginase. Asparaginase kills cancer cells by depleting a certain protein in the blood (L-asparagine) that is necessary for survival and growth of tumor cells in patients with ALL. Fortunately, normal cells are not dependent on L-asparagine for survival.
Asparaginase is mainly given in combination with vincristine and steroids (either prednisone or dexamethasone) for the first three weeks of therapy.
Recommended Dosage
Adults and Children
Induction Chemotherapy for All
Doses vary between different chemotherapy protocols. The usual dose is 6,000-10,000 units per square meter of body surface area given for 10 days. Patients should refer to individual protocol for recommended dose.
Administration
This medicine can be given directly into the muscle (intramuscular) or into the vein (intravenous). Intramuscular injection of asparaginase lowers the risk of severe allergic reactions (also known as hypersensitivity or anaphylaxis). The risk of hypersensitivity reaction is higher with the second and third dose of the drug.
Precautions
The use of this medication should be avoided in patients with active pancreatitis (inflammation of the pancreas) or history of pancreatitis, and in patients with serious allergic reaction to asparaginase in the past.
Asparaginase should only be given in a hospital. A patient's blood pressure will need to be monitored every 15 minutes for the first hour. A small test dose may be given to check if patient is allergic to this medicine.
This medication can lower the body's ability to fight infections. Patients should avoid contact with crowds or any individual that may have an infection.
Breast-feeding mothers should use asparaginase with caution. It is not yet known whether this drug crosses into breast milk. Women who are pregnant or may become pregnant should avoid this drug unless the benefits to the mother outweigh the risks to the child.
Contact a doctor immediately if any of these symptoms develop:
- fever, chills, sore throat
- yellowing of the skin or eyes
- puffy face, skin rash, trouble breathing, joint pain
- drowsiness, confusion, hallucinations, convulsions
- unusual bleeding or bruising
- stomach pain with nausea, vomiting and loss of appetite
A physician will perform blood tests before starting therapy and during therapy to monitor complete blood count, blood sugar, and pancreas, kidney, and liver functions.
Side Effects
Asparaginase is a very potent medicine that can cause serious side effects. An allergic reaction with skin rash, itching, joint pain, puffy face, and difficulty breathing can occur very quickly after injection with his drug. This side effect is managed by having the drugs epinephrine, diphenhydramine, and steroids available near the bedside to counter the allergic reaction if it occurs. Other common side effects include nausea, vomiting, diarrhea, loss of appetite, stomach cramps, and yellowing of the eyes or skin. Less frequent side effects include high blood sugar, drowsiness, confusion, hallucinations, convulsions, decreased kidney function, increased blood clotting, mouth sores, and decreased ability to fight infections. Usually the side effects of asparaginase are more severe in adults than in children.
Interactions
Asparaginase can decrease effectiveness of methotrexate in killing cancer cells when given right before and together with methotrexate. The use of these two medicines together should be avoided.
Asparaginase can decrease breakdown and increase toxicity of cyclophosphamide.
Risk of liver disease may be increased in patients receiving both asparaginase and mercaptopurine.
This medicine can increase blood sugar especially when given in together with steroids.
Asparaginase should be given after vincristine instead of before or with vincristine because it can increase the risk of numbing, tingling and pain in hands and feet.
—Olga Bessmertny, Pharm.D.
Oxford Dictionary of Biochemistry:
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asparaginase
EC 3.5.1.1; other names: l-asparaginase; systematic name: l-asparagine amidohydrolase; an enzyme that catalyses the hydrolysis of l-asparagine to l-aspartate and NH3. It is an effective antileukemic drug when injected into the bloodstream, its action being to deprive fast-growing tumour cells of the exogenous asparagine they require for rapid growth. Its clinical usefulness is limited because it causes damage to tissues with low asparagine synthetase activity. Several isoenzymes are found in several bacteria.
| asialo+, asexual reproduction, aseptic technique | |
| asparaginate, asparagine, asparagine repeat |
Saunders Veterinary Dictionary:
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asparaginase
An enzyme that catalyzes the deamination of asparagine; used as an antineoplastic agent against cancers, e.g. acute lymphocytic leukemia, in which the malignant cells require exogenous asparagine for protein synthesis.
Wikipedia on Answers.com:
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Asparaginase
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|---|---|
| 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) |
| Routes | intramuscular, subcutaneous, or intravenous |
| Pharmacokinetic data | |
| Half-life | 8-30 hrs |
| Identifiers | |
| CAS number | 9015-68-3  |
| ATC code | L01XX02 |
| DrugBank | DB00023 |
| UNII | G4FQ3CKY5R |
| KEGG | D02997 |
| Chemical data | |
| Formula | C1377H2208N382O442S17 |
| Mol. mass | 31731.9 g/mol |
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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.
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Contents
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Use
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 as a food processing aid to reduce the formation of acrylamide, a suspected carcinogen, in starchy food products such as snacks and biscuits.[1]
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 most of other chemotherapy agents, it can be given as an intramuscular, subcutaneous, or intravenous injection without fear of tissue irritation.
Mechanism of action
As a food processing aid
The carcinogen acrylamide is often formed in starchy foods when they are baked or fried: 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. Unfortunately, carcinogens such as acrylamide and some heterocyclic amines in also formed in 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.[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]
As a drug
The rationale behind asparaginase is that it takes advantage of the fact that ALL leukemic 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. 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.[5]
Enzyme regulation
This protein may use the morpheein model of allosteric regulation.[6]
Side effects in drug use
The main side effect is an allergic or hypersensitivity reaction; anaphylaxis is a possibility.[2] 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.[8]
Other common side effects include pancreatitis.
History
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.[9] Later it was found out that it is not the serum itself which provoke the tumour regression, but rather the enzyme asparaginase.[10]
After researches comparing different kinds of asparaginases, the one derived from Escherichia coli and Erwinia chrysanthemi turned out to have better 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] Asparaginase produced by Erwinia chrysanthemi instead is known as crisantaspase (BAN), and is available in the United Kingdom under the trade name Erwinase.[2]
References
- ^ 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 978-0-85369-845-6.
- ^ Appel IM, van Kessel-Bakvis C, Stigter R, Pieters R (2007). "Influence of two different regimens of concomitant treatment with asparaginase and dexamethason] 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.
- ^ Broome, J. D. (1981). "L-Asparaginase: Discovery and development as a tumor-inhibitory agent". Cancer treatment reports 65 Suppl 4: 111–114. PMID 7049374.
- ^ T. Selwood and E. K. Jaffe. (2011). "Dynamic dissociating homo-oligomers and the control of protein function.". Arch. Biochem. Biophys. 519 (2): 131–43. DOI:10.1016/j.abb.2011.11.020. PMID 22182754. http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=22182754.
- ^ a b Müller, H. (1998). "Use of L-asparaginase in childhood ALL". Critical Reviews in Oncology/Hematology 28 (2): 97–11. DOI:10.1016/S1040-8428(98)00015-8.
- ^ Johnston, P. G.; Hardisty, R. M.; Kay, H. E.; Smith, P. G. (1974). "Myelosuppressive effect of colaspase (L-asparaginase) in initial treatment of acute lymphoblastic leukaemia". British medical journal 3 (5923): 81–83. PMC 1611087. PMID 4604804. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=1611087.
- ^ Kidd, J. G. (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): 565–582. PMC 2136344. PMID 13109110. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2136344.
- ^ Broome, J. D. (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. PMC 2137570. PMID 14015821. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2137570.
External links
- Eukaryotic Linear Motif resource motif class CLV_TASPASE1
- Asparaginase at the US National Library of Medicine Medical Subject Headings (MeSH)
- Crisantaspase information from Macmillan Cancer Support
- U.S. NLM, NIH Drug Information Portal - Asparaginase
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Copyrights:
American Heritage Dictionary
The American Heritage® Dictionary of the English Language, Fourth Edition Copyright © 2007, 2000 by Houghton Mifflin Company. Updated in 2009. Published by Houghton Mifflin Company. All rights reserved.
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Gale Encyclopedia of Cancer
Gale Encyclopedia of Cancer. Copyright © 2006 by The Gale Group, Inc. All rights reserved.
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Oxford Dictionary of Biochemistry
Oxford University Press. Oxford Dictionary of Biochemistry and Molecular Biology © 1997, 2000, 2006 All rights reserved.
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Saunders Veterinary Dictionary
Saunders Comprehensive Veterinary Dictionary 3rd Edition. Copyright © 2007 by D.C. Blood, V.P. Studdert and C.C. Gay, Elsevier. All rights reserved.
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