Asparaginase
Asparaginase is an enzyme that is used as a medication and in food manufacturing. As a medication, L-asparaginase is used to treat acute lymphoblastic leukemia (ALL). It is given by injection into a vein, muscle, or under the skin. A pegylated version is also available. In food manufacturing it is used to decrease acrylamide.Common side effects when used by injection include allergic reactions, pancreatitis, blood clotting problems, high blood sugar, kidney problems, and liver dysfunction. Use in pregnancy may harm the baby. As a food it is generally recognized as safe. Asparaginase works by breaking down the amino acid known as asparagine without which the cancer cells cannot make protein.The most common adverse reactions of asparaginase erwinia chrysanthemi (recombinant)-rywn include abnormal liver tests, nausea, musculoskeletal pain, fatigue, infection, headache, pyrexia, drug hypersensitivity, febrile neutropenia, decreased appetite, stomatitis, bleeding, and hyperglycemia.Asparaginase was approved for medical use in the United States in 1978. It is on the World Health Organizations List of Essential Medicines. It is often made from Escherichia coli (E. coli) or Erwinia chrysanthemi.

Uses
Asparaginases can be used for different industrial and pharmaceutical purposes.

Medical
E. coli strains are the main source of medical asparaginase. Branded formulations (with different chemical and pharmacological properties) available in 1998 include Asparaginase Medac, Ciderolase, and Oncaspar.: 5  (Crasnitin has been discontinued.) Spectrila is a recombinant E. coli asparaginase.Asparaginase produced by Dickeya dadantii (formerly called Erwinia chrysanthemi) instead is known as crisantaspase (BAN), and is available in the United Kingdom under the brand name Erwinase.One of the E. coli asparaginases marketed under the brand name Elspar for the treatment of acute lymphoblastic leukemia (ALL) is also used in some mast cell tumor protocols.On 30 June 2021, the U.S. Food and Drug Administration (FDA) approved asparaginase erwinia chrysanthemi (recombinant)-rywn) as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL) in people aged one month or older who have developed hypersensitivity to E. coli-derived asparaginase. The FDA granted the application for asparaginase erwinia chrysanthemi (recombinant)-rywn fast track and orphan drug designations.

Food manufacturing
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.

Side effects
The main side effect is an allergic or hypersensitivity reaction; anaphylaxis is a possibility. 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. Bone marrow suppression is common but only mild to moderate, rarely reaches clinical significance and therapeutic consequences are rarely required.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
As a food processing aid
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.As a food processing aid, asparaginases can effectively reduce the level of acrylamide in a range of starchy foods without changing the taste and appearance of the end product.

As a drug
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. 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.

Enzyme regulation
Type I L-asparaginase protein may use the morpheein model of allosteric regulation.

Cost
Normal asparaginase costs less than its pegylated version, pegaspargase.  However, because it doesnt 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.

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. Later it was found out that it is not the serum itself which provoke the tumour regression, but rather the enzyme asparaginase.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.

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

References
External links
Eukaryotic Linear Motif resource motif class CLV_TASPASE1
Asparaginase at the US National Library of Medicine Medical Subject Headings (MeSH)
"Asparaginase". Drug Information Portal. U.S. National Library of Medicine.
Clinical trial number NCT04145531 for "An Open-Label Study of JZP-458 (RC-P) in Patients With Acute Lymphoblastic Leukemia (ALL)/Lymphoblastic Lymphoma (LBL)" at ClinicalTrials.gov