Asparaginase derived from Escherichia coli (L-asparagine amidohydrolase, EC 22.214.171.124) is an enzyme responsible for the metabolism of L-asparagine, by catalyzing L-asparagine into L-aspartic acid and ammonia. It also facilitates the production of oxaloacetate which is needed for general cellular metabolism.
<0.001 EU per 1 μg of the protein by the LAL method
Lyophilized protein should be stored at < -20°C, though stable at room temperature for 3 weeks. Reconstituted protein solution can be stored at 2-8 °C for 1 week. Aliquots of reconstituted samples are stable at < -20°C for 3 months.
Asparaginase Escherichia coli
Indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia (ALL).
Examples of Clinical Use:
Acute lymphoblastic leukemia (ALL)
In clinical trials of patients with previously untreated, standard-risk ALL, administration of asparaginase resulted in a decrease of plasma asparagine levels from average of 41 μM to less than 3 μM. The native asparaginase in whom plasma enzyme activity before treatment was greater than 0.1 International Units/mL. In this study, cerebrospinal fluid asparagine levels in patients treated with asparaginase decreased from 2.8 μM (pretreatment) to 1.0 μM and 0.3 μM at day 7 and day 28 of induction, respectively. Native E. coli asparaginase results in asparagine depletion in 14 to 23 days following administration.
Mechanism of action:
Asparagine is a non-essential amino acid that maintains DNA, RNA and protein synthesis and promotes cell growth. While healthy and normal cells are capable of obtaining asparagine via dietary intake or synthesizing the asparagine from aspartate via asparagine synthetase activity, lymphoblastic leukemic cells lack the asparagine synthetase enzyme and cannot produce asparagine de novo. Thus, leukemic cells rely on exogenous source of asparagine for protein synthesis and cell survival. L-asparagine from E. coli serves to deplete plasma levels of asparagine in leukemic cells by converting L-asparagine to L-aspartic acid and ammonia, leading to reduced reduced DNA, RNA and protein synthesis; inhibition of cell growth; and ultimately the activation of apoptotic cell-death mechanisms. Normal cells, however, are able to synthesize asparagine and thus are affected less by the rapid depletion produced by treatment with the enzyme asparaginase.
Asparaginase is an enzyme that hydrolyzes asparagine to produce aspartic acid and ammonia (NH3). This enzyme is found in many organisms, such as bacteria, fungi, plants, and animals. According to the different sources and characteristics, asparaginase can be divided into asparaginase I from Escherichia coli, asparaginase II from Escherichia coli, asparaginase from bovine testis, and asparaginase from yeast. Among them, Asparaginase I(Asparaginase Escherichia coli) from Escherichia coli is an N-acyltransferase that catalyzes the synthesis of N-acylaspartamide from asparagine and fatty acyl-CoA. This enzyme is one of the important drugs in the treatment of acute lymphoblastic leukemia (ALL) because it is able to hydrolyze the plasma asparagine to aspartic acid, thereby destroying the demand for asparagine in leukemia cells and inhibiting their growth. In addition, asparaginase can also be used to synthesize n-acyl asparagine, which is an important intermediate in organic synthesis. In synthesis, asparaginase can catalyze the acylation of asparagine with fatty acyl-CoA to produce n-acyl-asparagine. This intermediate can be used to synthesize a variety of drugs and bioactive substances.
Clinical Application of Asparaginase
Asparaginase Escherichia coli's primary use is to treat acute lymphoblastic leukemia (ALL), a common type of leukemia. Asparaginase can hydrolyze the plasma asparagine to aspartic acid, thus destroying the demand for asparagine in leukemia cells and inhibiting its growth. Therefore, it is used as one of the important drugs in the treatment of acute lymphoblastic leukemia. In addition to treating acute lymphoblastic leukemia, asparaginase can also be used to synthesize n-acyl asparagine, which is an important intermediate in organic synthesis. In synthesis, asparaginase can catalyze the acylation of asparagine with fatty acyl-CoA to produce n-acyl-asparagine. This intermediate can be used to synthesize a variety of drugs and bioactive substances. In summary, Asparaginase Escherichia coli has a wide range of clinical applications, not only for the treatment of acute lymphoblastic leukemia but also for the synthesis of organic compounds.
Action mechanism of Asparaginase
Asparaginase Escherichia coli's mechanism of action is to destroy the demand for asparagine by catalytic hydrolysis of asparagine, thus inhibiting the growth of leukemia cells. Specifically, Asparaginase Escherichia coli can split plasma asparagine into aspartic acid and ammonia in a reaction that consumes one molecule of water. Under physiological conditions, the activity of asparaginase is affected by many factors such as substrate concentration, pH value, temperature, inhibitor, and activator. Among them, the concentration of substrate has the greatest influence on the activity of asparaginase. When the concentration of substrate is low, the activity of the enzyme increases with the increase of the concentration of substrate, but when the concentration of substrate reaches a certain value, the activity of the enzyme no longer increases, and the activity of the enzyme reaches the maximum value. In addition, pH also has an important effect on the activity of asparaginase. Under acidic conditions, the activity of asparaginase is lower, while under alkaline conditions, its activity is higher. Therefore, in clinical applications, the pH value is usually controlled at about 7.5 to obtain the best therapeutic effect. In addition to the above factors, temperature, inhibitors, and activators can also affect the activity of asparaginase. For example, excessive temperature can cause enzyme denaturation and inactivation, while some inhibitors such as sulfonamides inhibit enzyme activity. In contrast, some activators such as choline and ascorbic acid increase enzyme activity. In conclusion, Asparaginase Escherichia coli treats acute lymphoblastic leukemia by catalyzing asparagine hydrolysis, and its mechanism is influenced by various factors. In clinical application, these factors need to be considered comprehensively to obtain the best therapeutic effect.
Advantages and Disadvantages of Asparaginase
Asparaginase Escherichia coli has the following advantages in clinical application: It is effective against acute lymphoblastic leukemia (ALL) and can significantly improve the survival rate of patients; Can be large-scale production through E. coli, low manufacturing cost, the price is relatively close to the people; In clinical use, Asparaginase Escherichia coli has a low incidence of allergic reactions and a high safety. However, Asparaginase Escherichia coli has some drawbacks in clinical application: frequent injection is required for clinical application, which brings great inconvenience to patients; Some patients may have drug resistance, which affects the therapeutic effect. There are some side effects and adverse reactions, such as headache, nausea, vomiting, allergic reactions, etc. To sum up, Asparaginase Escherichia coli has certain advantages and value in clinical application, but there are still some areas that need to be improved and perfected.
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