Kuldeep Kumar

L-Asparaginase: A Promising Chemotherapeutic Agent

ABSTRACT This article comprises detailed information about L-asparaginase, encompassing topics such as microbial and plant sources of L-asparaginase, treatment with L-asparaginase, mechanism of action of L-asparaginase, production, purification, properties, expression and characteristics of l-asparaginase along with information about studies on the structure of L-asparaginase. Although L-asparaginase has been reviewed by , our effort has been to include recent and updated information about the enzyme covering new aspects such as structural modification and immobilization of L-asparaginase, recombinant L-asparaginase, resistance to L-asparaginase, methods of assay of L-asparagine and L-asparaginase activity using the biosensor approach, L-asparaginase activity in soil and the factors affecting it. Also, side-effects of L-asparaginase treatment in acute lymphoblastic leukemia (ALL) have been discussed in the current review. L-asparaginase has been and is still one of the most widely studied therapeutic enzymes by researchers and scientists worldwide.

E. coli K-12 Asparaginase-Based Asparagine Biosensor for Leukemia

The present work aims at the development of a novel, diagnostic biosensor for monitoring asparagine levels in leukemia. Various immobilization strategies have been applied to improve the stability of the biocomponent (asparaginase). Response time studies have been carried out for different immobilization methods. Phenol Red indicator has been coimmobilized with asparaginase and color visualization approach has been optimized for various asparagine ranges. The detection limit of asparagine achieved with nitrocellulose membrane is 10−1 M, with silicon gel is 10−10–10−1 M, and with calcium alginate beads is 10−9–10−1 M. Furthermore, the calcium alginate bead system of immobilization has been applied for the asparagine range detection in normal and leukemia serum samples.

Plant asparaginase-based asparagine biosensor for leukemia

Abstract The present work aims at the development of plant asparaginase-based asparagine biosensor for leukemia. It is a novel diagnostic for monitoring asparagine levels in patients suffering from acute lymphoblastic leukemia (ALL). Various immobilization strategies have been applied to improve the stability of the asparaginase. The latest and updated information including some new techniques of immobilization related to L-asparaginase such as gelatin, agarose, agar, and calcium alginate methods are described in detail along with response time studies and comparative data. Furthermore these immobilization techniques have been applied for the detection of asparagine in normal and leukemia serum samples.

l-asparaginase: an effective agent in the treatment of acute lymphoblastic leukemia

Abstract l-asparaginase (L-ASNase) is an enzyme used most effectively in the treatment of acute lymphoblastic leukemia (ALL) for more than 30 years. It catalyzes the hydrolysis of amino acid l-asparagine to aspartic acid and ammonia, which leads to cell death. Clinical trials have been conducted using L-ASNase in combination with other drugs and radiotherapy, which have led to great success in the treatment of ALL. Treatments consist of induction therapy and central nervous system therapy. The achievement of complete remission in patients is associated with a few side-effects of using l-asparaginase, including pancreatitis, coagulation abnormalities and allergic reactions. Sometimes tumor cells may develop resistance to L-ASNase. To overcome these difficulties, the drug is modified by pegylation or immobilization, and also treatment protocols can be modified to increase the efficiency of the drug.

COMPARATIVE CHARACTERIZATION OF L-ASPARAGINASE EXTRACTED FROM PLANT AND MICROBIAL SOURCES

L-asparaginase has been used for the treatment of different leukemia such as Acute Lymphoblastic Leukemia. Unlike normal cells leukemic cells cannot synthesize asparagine on their own. Therefore, when L-asparaginase is injected into blood it breaks down asparagine to aspartic acid and ammonia and hence tumor cells die due to asparagine starvation. It is produced by both microbes as well as plants. Therefore, in the present study we compared the L-asparaginase extracted from plants as well as microbes. Among the plants S. nigrum showed the highest activity (52 IU/ml) whereas among microbes B. subtilis (MTCC-121) had the highest activity (43.11 IU/ml). Both the enzymes were kinetically characterized and it was found that plant enzyme was stable over pH and temperature variations. The effect of metal ions was same on both the enzymes whereas chelators enhanced the plant enzyme whereas had no effect on microbial enzyme. Plant enzyme showed the highest activity and was more stable to the environmental variations as compared to microbial enzyme.