Asparaginase

Asparaginase (EC 3.5.1.1, USAN) or Colaspase (BAN) is an enzyme widely applied as medication and in food manufacturing. Asparaginase is competent to break down the amino acid known as asparagine, whose absence could block the cancer cells to synthesize protein. Asparaginase is approved for medical use in the United States in 1978, listed on the World Health Organization's List of Essential Medicines and announced to be one of the most effective and safe medicines needed in a health system. In medicinal field, diseases like acute lymphoblastic leukemia, acute myeloid leukemia, and non-Hodgkin's lymphoma can be treated by L-asparaginase, which is given by injection into a vein, muscle, or under the skin. A pegylated version of asparaginase is also available. As an assistant in food manufacturing, asparaginase is generally used to decrease acrylamide.

Names

Asparaginase is a United States Adopted Name (USAN) and could also be called crisantaspase and colaspase, where crisantaspase is British Approved Name (BAN) for asparaginase produced from Erwinia chrysanthemi and colaspase is the BAN of asparaginase extracted from Escherichia coli. The brand names of colaspase are Elspar, Kidrolase, Leunase and Spectrila, while Erwinase and Erwinaze are brand names for crisantaspase. The pegylated version of colaspase is called pegaspargase, whose brand name is Oncaspar.

History

The gradual development of asparaginase as an anti-cancer agent initiates in 1953, when lymphomas in rat and mice are regressed after treatment with guinea pig serum for the first time. Later researches find that it is the enzyme asparaginase that provokes the tumour regression, instead of the serum itself. Asparaginase is often obtained from Escherichia coli or Erwinia chrysanthemi. By comparing different kinds of asparaginases, the ones from Escherichia coli and Erwinia chrysanthemi turn out to display optimum anti-cancer ability. As a result, Escherichia coli become the main source of asparaginase since it is easy to produce in large amount.

Applications

Asparaginases can be applied for different industrial and pharmaceutical purposes. Branded formulations with different chemical and pharmacological properties are available in 1998 mainly including Asparaginase Medac, Ciderolase, and Oncaspar, Spectrila (a new recombinant asparaginase from Escherichia coli). Asparaginase produced by Erwinia chrysanthemi also known as crisantaspase (BAN) is traded as Erwinase in the United Kingdom. One of the Escherichia coli asparaginases with a brand name Elspar in the treatment of acute lymphoblastic leukemia is also effective in some mast cell tumor protocols. Asparaginase is different from most of other chemotherapy agents by being given as an intramuscular, subcutaneous, or intravenous injection free from tissue irritation. The most common use of asparaginases is functioning as a processing assitant in food manufacturing. Commercial available Acrylaway and PreventASe of asparaginases have been exploited as a food processing aid to inhibit the formation of acrylamide that is a suspected carcinogen in starchy food such as snacks and biscuits.

Mechanism of Action

Asparaginase as a drug could take advantage of the fact that acute lymphoblastic leukemia cells and some other suspected tumor cells are incapable of synthesizing the non-essential amino acid asparagine, while normal cells could produce their own asparagine. Therefore, leukemic cells mainly depend on circulating asparagine and call for large amount of asparagine, which can be catalyzed by asparaginase to converse into aspartic acid and ammonia, thus depriving the circulating asparagine needed by leukemic cell and leading to cell death.

When heated, asparagine naturally present in starchy foods undergoes a process called Maillard reaction, which is responsible for the brown color, crust, and toasted flavor of the baked or fried foods and simultaneously generates some suspected carcinogens such as acrylamide and some heterocyclic amines. Before baking or frying the food, the adding of asparaginase could convert asparagine into another common amino acid, aspartic acid, and ammonium. Asparagine thereby cannot take part in the Maillard reaction, and consequently the formation of acrylamide is significantly controlled. As a food processing assistant, asparaginases can efficiently diminish the level of acrylamide up to 90% in various starchy foods without changing the taste and appearance of the final product. The complete removal of acrylamide is probably not possible due to the existence of other minor asparagine-independent formation pathways.

Side Effects

The main adverse effect of asparaginase is the induced allergic or hypersensitivity reaction, which possibly causes anaphylaxis. Furthermore, asparaginase is also associated with coagulopathy for it inhibits protein synthesis, including the synthesis of coagulation factors and anticoagulant factor, thus leading to bleeding or thrombotic events such as stroke. The suppression of bone marrow is also a common concomitant, but only in a mild to moderate degree, rarely reaching clinical significance and therapeutic consequences. Pancreatitis is also an accompanying side effect, which mainly attributes to the dual activity of L-asparaginase since it is also able to hydrolyze L-glutamine to glutamic acid and ammonia. Other common side effects caused by injection include blood clotting problems, high blood sugar, kidney problems, and liver dysfunction. The application during pregnancy may be harmful to the baby. It is generally recognized as safe to be a food.

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