Asparaginase
Encyclopedia
Asparaginase is an enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...

 that catalyzes the hydrolysis
Hydrolysis
Hydrolysis is a chemical reaction during which molecules of water are split into hydrogen cations and hydroxide anions in the process of a chemical mechanism. It is the type of reaction that is used to break down certain polymers, especially those made by condensation polymerization...

 of asparagine
Asparagine
Asparagine is one of the 20 most common natural amino acids on Earth. It has carboxamide as the side-chain's functional group. It is not an essential amino acid...

 to aspartic acid
Aspartic acid
Aspartic acid is an α-amino acid with the chemical formula HOOCCHCH2COOH. The carboxylate anion, salt, or ester of aspartic acid is known as aspartate. The L-isomer of aspartate is one of the 20 proteinogenic amino acids, i.e., the building blocks of proteins...

. 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. Marketed under the brand names Acrylaway and PreventASe, asparaginases are used to reduce the formation of acrylamide
Acrylamide
Acrylamide is a chemical compound with the chemical formula C3H5NO. Its IUPAC name is prop-2-enamide. It is a white odourless crystalline solid, soluble in water, ethanol, ether, and chloroform. Acrylamide is incompatible with acids, bases, oxidizing agents, iron, and iron salts...

, 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
Acute lymphoblastic leukemia
Acute lymphoblastic leukemia is a form of leukemia, or cancer of the white blood cells characterized by excess lymphoblasts.Malignant, immature white blood cells continuously multiply and are overproduced in the bone marrow. ALL causes damage and death by crowding out normal cells in the bone...

 (ALL) and is also used in some mast cell tumor protocols. 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
Escherichia coli
Escherichia coli is a Gram-negative, rod-shaped bacterium that is commonly found in the lower intestine of warm-blooded organisms . Most E. coli strains are harmless, but some serotypes can cause serious food poisoning in humans, and are occasionally responsible for product recalls...

. Asparaginase produced by Erwinia chrysanthemi instead is known as crisantaspase (BAN
British Approved Name
A British Approved Name is the official non-proprietary or generic name given to a pharmaceutical substance, as defined in the British Pharmacopoeia...

), and is available in the United Kingdom
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...

 under the trade name Erwinase.

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
Amino acid
Amino acids are molecules containing an amine group, a carboxylic acid group and a side-chain that varies between different amino acids. The key elements of an amino acid are carbon, hydrogen, oxygen, and nitrogen...

 asparagine
Asparagine
Asparagine is one of the 20 most common natural amino acids on Earth. It has carboxamide as the side-chain's functional group. It is not an essential amino acid...

, naturally present in starchy foods, is converted into acrylamide in a process called the Maillard reaction
Maillard reaction
The Maillard reaction is a form of nonenzymatic browning similar to caramelization. It results from a chemical reaction between an amino acid and a reducing sugar, usually requiring heat....

. 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
Aspartic acid
Aspartic acid is an α-amino acid with the chemical formula HOOCCHCH2COOH. The carboxylate anion, salt, or ester of aspartic acid is known as aspartate. The L-isomer of aspartate is one of the 20 proteinogenic amino acids, i.e., the building blocks of proteins...

, and ammonium
Ammonium
The ammonium cation is a positively charged polyatomic cation with the chemical formula NH. It is formed by the protonation of ammonia...

. 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 up to 90% in a range of starchy foods without changing the taste and appearance of the end product.

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
Adverse effect (medicine)
In medicine, an adverse effect is a harmful and undesired effect resulting from a medication or other intervention such as surgery.An adverse effect may be termed a "side effect", when judged to be secondary to a main or therapeutic effect. If it results from an unsuitable or incorrect dosage or...

 is an allergic or hypersensitivity reaction; anaphylaxis
Anaphylaxis
Anaphylaxis is defined as "a serious allergic reaction that is rapid in onset and may cause death". It typically results in a number of symptoms including throat swelling, an itchy rash, and low blood pressure...

 is a possibility. Asparaginase has also been associated with pancreatitis
Pancreatitis
Pancreatitis is inflammation of the pancreas. It occurs when pancreatic enzymes that digest food are activated in the pancreas instead of the small intestine. It may be acute – beginning suddenly and lasting a few days, or chronic – occurring over many years...

. Additionally, it can also be associated with a coagulopathy
Coagulopathy
Coagulopathy is a condition in which the blood’s ability to clot is impaired. This condition can cause prolonged or excessive bleeding, which may occur spontaneously or following an injury or medical and dental procedures.The normal clotting process depends on the interplay of various proteins in...

 as it decreases protein synthesis, including synthesis of coagulation factors (eg progressive isolated decrease of fibrinogen
Fibrinogen
Fibrinogen is a soluble plasma glycoprotein, synthesised by the liver, that is converted by thrombin into fibrin during blood coagulation. This is achieved through processes in the coagulation cascade that activate the zymogen prothrombin to the serine protease thrombin, which is responsible for...

) and anticoagulant factor (generally antithrombin
Antithrombin
Antithrombin is a small protein molecule that inactivates several enzymes of the coagulation system. Antithrombin is a glycoprotein produced by the liver and consists of 432 amino acids. It contains three disulfide bonds and a total of four possible glycosylation sites...

 III; sometimes protein C
Protein C
Protein C, also known as autoprothrombin IIA and blood coagulation factor XIV, is a zymogenic protein, the activated form of which plays an important role in regulating blood clotting, inflammation, cell death and maintaining the permeability of blood vessel walls in humans and other animals...

 & S
Protein S
Protein S is a vitamin K-dependent plasma glycoprotein synthesized in the endothelium. In the circulation, Protein S exists in two forms: a free form and a complex form bound to complement protein C4b. In humans, protein S is encoded by the PROS1 gene...

 as well), leading to bleeding
Bleeding
Bleeding, technically known as hemorrhaging or haemorrhaging is the loss of blood or blood escape from the circulatory system...

 or thrombotic events such as stroke.

External links

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