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The objective of the study described the importance of L-asparaginase and its importance in the field of medicine. Different types of enzymes are produced based on the adaptation to the environment where the living organisms live to tune the metabolic pathways according to their adapted changes. The enzymes present in various organs are produced by...
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The objective of the study described the importance of L-asparaginase and its importance in the field of medicine. Different types of enzymes are produced based on the adaptation to the environment where the living organisms live to tune the metabolic pathways according to their adapted changes. The enzymes present in various organs are produced by...
Citations
... In cancer cells, asparaginase is lacking and treating the patient with asparaginase helps in hydrolysing serum asparagines (Cachumba et al., 2016) . This enzyme can be produced from different microbial sources such as bacteria, fungi, yeast and actinomycetes (Prasad et al., 2014). It can also be isolated from soil microflora. ...
This study aims at investigating the soil bacteria for L asparaginase enzyme production and its anti-cancer effect on MCF 7 cell line. In this study, 30 soil samples were screened for bacterial producing L asparaginase enzyme. The soil samples were collected from various places in Ethiraj College, Chennai. Isolation was done using spread plate technique, biochemical and microscopic characterization for the potential isolates revealed the bacterial genera as Bacillus, Escherichia and Pseudomonas species. Of the thirty samples collected, six isolates produced pronounced L asparaginase enzyme. These samples were further subjected to crude enzyme extraction and estimation. The isolates S2 and Ni5 showed maximum production of enzyme with 1090 units/ml of activity. Dialysis was carried out to concentrate the enzyme and molecular characterization was performed using SDS PAGE to separate the proteins according to the molecular weight which was found to be approximately 100 to 116 kDa. Anti-cancer activity was evaluated on MCF 7 tumour cell line. The cell viability was dose dependent and IC 50 of S2 was 62.5 µg and Ni5 31.2 µg respectively.
... These DNA damages degrade the level of ASNase in the cell membrane, leading to depletion of its concentration followed by protein dysfunction and cell death [31]. It is worth mentioning that the process of converting asparagine into aspartic acid by ASNase is followed by an enhancement in oxidation levels and a lessening in the reduction state [32]. This oxidation state has the potential to increase ROS levels and cause DNA damage [25], [26]. ...
BACKGROUND: Lisinopril is a medication used to lower blood pressure by inhibiting the angiotensin-converting enzyme (ACE). L-asparaginase is a chemotherapeutic agent used to treat acute lymphoblastic leukemia. AIM: To Study the effect of lisinopril on the genotoxicity of L-asparaginase (ASNase) in bone marrow stem cells. METHODS: Albino Swiss male mice were divided into three groups. The first group was treated with lisinopril 10 mg/kg/day for 14 days. The second group mice were injected with L-asparaginase 3000 IU/kg. The last group was treated with of lisinopril for 14 days followed with an intraperitoneal injection of L-asparaginase (ASNase) at the end of the 13th day. Genotoxicity was assessed by calculating the percentage of micronucleus (MN) and mitotic index (MI). RESULTS: ASNase significantly increased genotoxicity by raising the %MN and lowering % MI. When Lisinopril 10 mg/kg/day was administered no significant effect was seen. However, a significant decrease in genotoxic effects was observed when mice receiving Lisinopril were injected with 3000 IU/kg ASNase as compared the group treated with ASNase alone. This effect was manifested by decreasing %MN and increasing %MI. CONCLUSION: Using lisinopril for blood hypertension treatments concurrently with the cancer therapeutic agent, L- asparaginase, decreased its genotoxicity in bone marrow stem cells.
... The synergestic properties of bacterial glutaminase along with other compounds is reported when Pseudomonas 7A glutaminase was complexed with anticancer antibodies which when applied showed drastic effect as an antiproliferative compound against cancerous cells. By in vitro studies, the proliferative activity of glutaminase against cell lines can be possible to study through using MTT (3-(4, 5-dimethylthiazol-2-yl) -2, 5-diphenyltetrazolium bromide) assay (Prasad Talluri et al. 2014). In the case of marine Alcaligenes faecalis KLU102, they were able to inhibit the viability of HeLa cells in a specific dose, i.e. with an IC50 value of around 12.5 mg/ml in only a 24-h incubation period. ...
In the current scenario, considerable attention is being given to the enzyme L-glutaminase (EC 3.5.1.2). It belongs to the amidohydrolase class adherent to the family of serine-reliant β-lactamases and the penicillin-binding proteins due to its higher affinity to polymerize and modify peptidoglycan synthesis. However, based on the catalytic proficiency, L-glutaminase is characterized as a proteolytic endopeptidase that cleaves peptide linkage and emancipates various byproducts, viz. ammonia along with glutamate. L-glutamine is considered the key amino acid reportedly involved in multiple metabolic pathways such as nitrogen metabolism. The present review is focused on the recent development and aspects concomitant to the biotechnological applicability of L-glutaminase predominantly from the marine habitat. Additionally, a majority of L-glutaminases finds application in cancer therapy as therapeutic agents, especially for acute lymphocytic leukaemia. The in vitro studies have been effective against various human cancer cell lines. L-glutaminase enhances the growth of probiotic bacteria. Apart from all these applications, it is suitably applicable in fermented foods as a flavour enhancer especially the umami flavour and content. Marine habitats have largely been exploited for their bio-catalytic potential but very scarcely for therapeutic enzymes. Some of the reports of such marine bacterial isolates from Bacillus sp., Pseudomonas sp. and Vibrio sp. are in the domain, but none highlights the therapeutic applications predominantly as anticancer and anti-proliferative agents.
Key points
The exploration of marine habitats along the Gujarat coasts mainly for bacteria secreting L-glutaminase is scarcely reported, and even more scarce are the amidohydrolases from these marine niches as compared to their terrestrial counterparts.
Microbial sourced amidohydrolase has wide bio-applicability that includes food, cosmetics and therapeutics especially as anticancer/anti-proliferative agent making it of immense biotechnological significance.
... Various in vitro studies have also revealed the activity of glutaminase against the proliferation of tumor cell lines using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) cell proliferation assay [27,119,120]. A. faecalis KLU102 glutaminase was able to reduce the viability of HeLa cells in a dosedependent manner, with an IC 50 value of 12.5 mg/ml within a 24 h period [27]. Glutaminase from P. brevicompactum NRC 829 also suppressed the growth of human cell line hepatocellular carcinoma (Hep-G2), with an IC 50 value of 63.3 lg/ml [44]. ...
This article focuses on significant advances in the production and applications of microbial glutaminases and provides insight into the structures of different glutaminases. Glutaminases catalyze the deamidation of glutamine to glutamic acid, and this unique ability forms the basis of their applications in various industries such as pharmaceutical and food organizations. Microbial glutaminases from bacteria, actinomycetes, yeast, and fungi are of greater significance than animal glutaminases because of their stability, affordability, and ease of production. Owing to these notable benefits, they are considered to possess considerable potential in anticancer and antiviral therapy, flavor enhancers in oriental foods, biosensors and in the production of a nutraceutical theanine. This review also aims to fully explore the potential of microbial glutaminases and to set the pace for future prospects.
... L-asparaginase dapat ditemui pada jaringan hewan, tumbuhan, serta mikroorganisme (bakteri, fungi, dan khamir) (Talluri, Bhavana, Kumar, & Rajagopal, 2014). ...
L-asparaginase (EC 3.5.1.1) adalah enzim yang menghidrolisis asam amino L-asparagin menjadi amonia dan asam aspartat. Enzim ini mempunyai manfaat utama dalam bidang farmasi dan industri pangan. Enzim L-asparaginase tersebar secara luas pada mikroorganisme. Mikroorganisme yang mempunyai potensi menghasilkan enzim ini adalah mikroorganisme endofit dari tumbuhan mangrove. Penelitian ini bertujuan untuk mengisolasi dan mengidentifikasi bakteri endofit penghasil L-asparaginase dari tumbuhan mangrove Buta-buta (E. agallocha). Skrining dilakukan dengan menggunakan medium selektif untuk mendapatkan bakteri penghasil enzim L-asparaginase. Identifikasi molekuler dilakukan dengan menggunakan analisis filogenetik berdasarkan data sekuen 16S rDNA. Dari hasil penelitian ini didapatkan lima isolat bakteri endofit penghasil enzim L-asparaginase, di mana isolat penghasil L-asparaginase tertinggi diidentifikasi secara molekuler. Hasil identifikasi filogenetik molekuler menunjukkan bahwa isolat kode D.104 teridentifikasi sebagai Enterobacter cloacae.
... L-Asparaginase (asparagine amidohydrolase, EC 3.5.1.1, L-ASNase) is isolated from various (but not in humans) microorganisms such as bacteria, yeasts, fungi, actinomycetes that catalyzes the deamination of Lasparagine to L-aspartate and ammonia (NH 3 ) and to a minor extent also catalyzes the hydrolysis of L-glutamine to L-glutamate [20,21]. It has considerable potential in food and biotechnological application, but major percentage of the enzyme is used in medicine as chemotherapeutic drug. ...
The scope of our research was to prepare the organosilane-modified Fe3O4@MCM-41 core-shell magnetic nanoparticles,
used for L-ASNase immobilization and explored screening of immobilization conditions such as pH,
temperature, thermal stability, kinetic parameters, reusability and storage stability. In this content, Fe3O4 coreshell
magnetic nanoparticles were prepared via co-precipitation method and coated with MCM-41. Then,
Fe3O4@MCM-41 magnetic nanoparticles were functionalized by (3-glycidyloxypropyl) trimethoxysilane
(GPTMS) as an organosilane compound. Subsequently, L-ASNase was covalently immobilized on epoxyfunctionalized
Fe3O4@MCM-41 magnetic nanoparticles. The immobilized L-ASNase had greater activity at high
pH and temperature values. It alsomaintained N92% of the initial activity after incubation at 55 °C for 3 h. Regarding
kinetic values, immobilized L-ASNase showed a higher Vmax and lower Kmcompared to native L-ASNase. In
addition, it displayed excellent reusability for 12 successive cycles. After 30 days of storage at 4 °C and 25 °C,
immobilized L-ASNase retained 54% and 26% of its initial activities while native L-ASNase lost about 68% and
84% of its initial activity, respectively. As a result, the immobilization of L-ASNase onto magnetic nanoparticles
may provide an advantage in terms of removal of L-ASNase from reaction media.
... Important progress has been made in cancer chemotherapy include plant derived drugs with cytotoxic activity as the treatment of cancer [25,26,31]. Other workers [32,41]. Established natural products as anti-cancer properties in vivo or in vitro. ...
... On the other hand, total inhibition of all carcinoma cell lines proliferation and induction of 100% cell death has been observed in these cell lines after treatment with L-glutaminase at a concentration of 30 μg mL −1 with IC 50 for HEPG-2, MCF-7, and HCT-116 carcinoma equal to 4.0, 5.0, and 7.5 μg mL −1 , respectively (Fig. 5). In a previous studies, the cytotoxic power and antitumor activities of these enzymes found effective in countering acute lymphoblastic leukemia and they inhibited different human tumor cell lines such human hepatocellular carcinoma (HEPG-2), breast cancer cell line (MCF-7), colon cancer cell line (HCT-116), and human lung carcinoma (A-549) as reported by Unissa et al. [3] and Talluri et al. [46]. In spite of fungal secondary metabolites had emerged as appreciated sources of antioxidants, very few considerations focused on their enzymes including L-asparaginase and L-glutaminase as antioxidant agents. ...
Among all fungal endophytes isolates derived from different ethno-medical plants, the hyper-yield l-asparaginase and l-glutaminase wild strains Trichoderma sp. Gen 9 and Cladosporium sp. Gen 20 using rice straw under solid-state fermentation (SSF) were selected. The selected strains were used as parents for the intergeneric protoplast fusion program to construct recombinant strain for prompt improvement production of these enzymes in one recombinant strain. Among 21 fusants obtained, the recombinant strain AYA 20-1, with 2.11-fold and 2.58-fold increase in l-asparaginase and l-glutaminase activities more than the parental isolates Trichoderma sp. Gen 9 and Cladosporium sp. Gen 20, respectively, was achieved using rice straw under SSF. Both therapeutic enzymes l-asparaginase and l-glutaminase were purified and characterized from the culture supernatant of the recombinant AYA 20-1 strain with molecular weights of 50.6 and 83.2 kDa, respectively. Both enzymes were not metalloenzymes. Whereas thiol group blocking reagents such as p-chloromercurybenzoate and iodoacetamide totally inhibited l-asparaginase activity, which refer to sulfhydryl groups and cysteine residues involved in its catalytic activity, they have no effect toward l-glutaminase activity. Interestingly, potent anticancer, antioxidant, and antimicrobial activities were detected for both enzymes.
L-asparaginase (L-ASP) is one of the key enzymes used in therapeutic applications, particularly to treat Acute Lymphocytic Leukemia (ALL). L-asparagine is a non-essential amino acid, which means that it can be synthesized by the body and is not required to be obtained through the diet. The synthesis of L-asparagine occurs primarily in the liver, but it also takes place in other tissues throughout the body. In contrast, leukemic cells cannot synthesize L-asparagine due the absence of L-asparagine synthetase and should obtain it from circulating sources for protein synthesis and cell division processes to ensure their vital functions. L-ASP catalyzes the deamination process of L-asparagine amino-acid into aspartic acid and ammonia, depriving leukemic cells of asparagine. This leads to decreased protein synthesis and cell division in tumor cells. However, using L-ASP has side effects, such as hypersensitivity or allergic reaction, antigenicity, short half-life, temporary blood clearance, and toxicity. L-ASP immobilization can minimize the side effects of L-ASP by stopping the immune system from attacking non-human enzymes and improving the enzyme's performance. The first strategy includes modification of enzyme structure, such as covalent binding (conjugation), adsorption to the support material and cross-linking of the enzyme. The chemical modification of residues, often nonspecific, changes the enzyme's hydrophobicity and surface charge, lowering the enzyme's activity. Also, the first strategy exposes the enzyme's surface to the environment. This eliminates its performance and does not allow targeted delivery of the enzyme. The second strategy is based on the entrapment of the enzyme inside the protecting structure or encapsulation. This strategy offers the same benefits as the first. Still, it also enables reducing toxicity, prolonging in vivo half-life, enhancing stability and activity, enables a targeted delivery and controlled release of the enzyme. Compared to the first strategy, encapsulation does not modify the chemical structure of the enzyme since L-ASP is only effective against leukemia in its native tetrameric form. This review aims to present state of the art in L-ASP formulations developed for reducing the side effects of L-ASP, focusing on describing improvements in their safety. The primary focus in the field remains to be improving the overall performance of the L-ASP formulations. Almost all encapsulation systems allow reducing immune response due to screening the enzyme from antibodies and prolonging its half-life. However, the enzyme's activity and stability depend on the encapsulation system type. Therefore, the selection of the right encapsulation system is crucial in therapy due to its effect on the performance parameters of the L-ASP. Biodegradable and biocompatible materials, such as chitosan, alginate and liposomes, mainly attract the researcher's interest in enzyme encapsulation. The research trends are also moving towards developing formulations with targeted delivery and increased selectivity.
