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56-460: The one-letter symbol N for asparagine was assigned arbitrarily, with the proposed mnemonic asparagi N e; Asparagine was first isolated in 1806 in a crystalline form by French chemists Louis Nicolas Vauquelin and Pierre Jean Robiquet (then a young assistant). It was isolated from asparagus juice, in which it is abundant, hence the chosen name. It was the first amino acid to be isolated. Three years later, in 1809, Pierre Jean Robiquet identified

112-501: A transaminase enzyme converts to aspartate . The enzyme transfers the amino group from glutamate to oxaloacetate producing α-ketoglutarate and aspartate. The enzyme asparagine synthetase produces asparagine, AMP , glutamate, and pyrophosphate from aspartate, glutamine , and ATP . Asparagine synthetase uses ATP to activate aspartate, forming β-aspartyl-AMP. Glutamine donates an ammonium group, which reacts with β-aspartyl-AMP to form asparagine and free AMP. In reaction that

168-483: A food processing aid, asparaginases can effectively reduce the level of acrylamide in a range of starchy foods without changing the taste and appearance of the end product. Applications of asparaginase in cancer therapy take advantage of the fact that acute lymphoblastic leukemia cells and some other suspected tumor 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

224-581: A 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, which leads to cell death . Type I L-asparaginase protein may use the morpheein model of allosteric regulation . The discovery and development of asparaginase as an anti-cancer drug began in 1953, when scientists first observed that lymphomas in rat and mice regressed after treatment with guinea pig serum . Later it

280-400: A promising candidate to address this critical issue. Asparaginases can be used for different industrial and pharmaceutical purposes. E. coli strains are the main source of medical asparaginase. Branded formulations (with different chemical and pharmacological properties) available in 1998 include Asparaginase Medac, Ciderolase, and Oncaspar. (Crasnitin has been discontinued.) Spectrila

336-428: A publication now in the public domain :  Chisholm, Hugh , ed. (1911). " Vauquelin, Louis Nicolas ". Encyclopædia Britannica (11th ed.). Cambridge University Press. Asparaginase Asparaginase is an enzyme that is used as a medication and in food manufacturing . As a medication, L-asparaginase is used to treat acute lymphoblastic leukemia (ALL) and lymphoblastic lymphoma (LBL). It

392-574: A red lead ore from Siberia . He also managed to get liquid ammonia at atmospheric pressure. Later with Fourcroy, he identified a metal in a platinum residue they called ‘ ptène ’, This name ‘ptene’ or ‘ptène’ was reported as an early synonym for osmium . Either together or successively he held the offices of inspector of mines, professor at the School of Mines and at the Polytechnic School, assayer of gold and silver articles, professor of chemistry in

448-453: A substance from liquorice root with properties which he qualified as very similar to those of asparagine, and which Plisson identified in 1828 as asparagine itself. The determination of asparagine's structure required decades of research. The empirical formula for asparagine was first determined in 1833 by the French chemists Antoine François Boutron Charlard and Théophile-Jules Pelouze ; in

504-437: A therapeutic agent for acute lymphoblastic leukemia has achieved significant milestones throughout the years. In 1963, asparaginase (ASNase) was identified as an effective antileukemic agent, and subsequent efforts were made to isolate it from bacterial sources and scale up production for clinical trials. Clinical testing with bacterial-derived ASNase commenced in 1966, and in 1978, E . coli –derived ASNase received approval from

560-493: Is a recombinant E. coli asparaginase. Asparaginase produced by Dickeya dadantii (formerly called Erwinia chrysanthemi ) instead is known as crisantaspase ( BAN ), and is available in the United Kingdom under the brand name Erwinase. One of the E. coli asparaginases marketed under the brand name Elspar for the treatment of acute lymphoblastic leukemia is also used in some mast cell tumor protocols. In July 2006,

616-502: Is an allergic or hypersensitivity reaction; anaphylaxis is a possibility. Additionally, it can also be associated with a coagulopathy as it decreases protein synthesis, including synthesis of coagulation factors (e.g. progressive isolated decrease of fibrinogen ) and anticoagulant factor (generally antithrombin III; sometimes protein C & S as well), leading to bleeding or thrombotic events such as stroke. Bone marrow suppression

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672-561: Is common but only mild to moderate, rarely reaches clinical significance and therapeutic consequences are rarely required. Acrylamide is often formed in the cooking of starchy foods. During heating the amino acid asparagine , naturally present in starchy foods, undergoes a process called the Maillard reaction , which is responsible for giving baked or fried foods their brown color, crust, and toasted flavor. Suspected carcinogens such as acrylamide and some heterocyclic amines are also generated in

728-684: Is converted in the liver to glycidamide , which is a possible carcinogen. Asparagine synthetase is required for normal development of the brain. Asparagine is also involved in protein synthesis during replication of poxviruses . The addition of N -acetylglucosamine to asparagine is performed by oligosaccharyltransferase enzymes in the endoplasmic reticulum . This glycosylation is involved in protein structure and function. Louis Nicolas Vauquelin Louis Nicolas Vauquelin FRS(For) H FRSE ( French pronunciation: [lwi nikɔla voklɛ̃] ; 16 May 1763 – 14 November 1829)

784-455: Is given by injection into a vein , or muscle . A pegylated version is also available. In food manufacturing it is used to decrease acrylamide . Common side effects when used by injection include allergic reactions , pancreatitis , blood clotting problems, high blood sugar, kidney problems , and liver dysfunction . Use in pregnancy may harm the baby. As a food it is generally recognized as safe . Asparaginase works by breaking down

840-485: Is important to note that the AEs leading to patient deaths were sepsis (cohort 1a, n = 1), aspiration pneumonia (cohort 1b, n = 1), and multiorgan failure (cohort 1b, n = 1). However, it was determined that none of these deaths were directly related to the administration of JZP-458. The findings indicate that the administration of JZP-458 exhibits effectiveness and a safety profile that aligns with other asparaginases. Therefore,

896-768: Is the BAN of asparaginase obtained from Escherichia coli . The United States Adopted Name of crisantaspase is asparaginase Erwinia chrysanthemi . Elspar, Kidrolase, Leunase and Spectrila are brand names for colaspase, while Erwinase and Erwinaze are brand names for crisantaspase. Oncaspar is the brand name of pegaspargase. Synonyms : (1) crisantaspase biobetter JZP-458, (2) RC-P JZP-458, (3) recombinant Asparaginase erwinia chrysanthemi JZP-458, (4) recombinant asparaginase Erwinia chrysanthemi-rywn, and (5) recombinant crisantaspase JZP-458. US brand name : Rylaze and Code name : (1) JZP 458, (2) JZP-458, (3) JZP458, and (4) PF743. Erwinase has shown promising efficacy and safety profiles in

952-408: Is the occurrence of adverse events (AEs) associated with asparaginase therapy. These AEs can range from mild to severe and may include hypersensitivity reactions, hepatotoxicity, pancreatitis, coagulation disorders, and thromboembolism. Therefore, understanding the safety profile of Erwinase is crucial in assessing its overall benefit-risk balance. The main efficacy outcome measure was demonstration of

1008-479: Is the reverse of its biosynthesis, asparagine is hydrolyzed to aspartate by asparaginase . Aspartate then undergoes transamination to form glutamate and oxaloacetate from alpha-ketoglutarate. Oxaloacetate, which enters the citric acid cycle (Krebs cycle). Heating a mixture of asparagine and reducing sugars or other source of carbonyls produces acrylamide in food. These products occur in baked goods such as French fries, potato chips, and toasted bread. Acrylamide

1064-596: The amino acid known as asparagine without which the cancer cells cannot make protein . The most common nonhematological adverse reactions of asparaginase erwinia chrysanthemi (recombinant) include abnormal liver test, nausea, musculoskeletal pain, infection, fatigue, headache, febrile neutropenia, pyrexia, hemorrhage (bleeding), stomatitis, abdominal pain, decreased appetite, drug hypersensitivity, hyperglycemia, diarrhea, pancreatitis, and hypokalemia. The most common side effects of asparaginase erwinia chrysanthemi (recombinant) when given in combination with chemotherapy for

1120-684: The Children's Oncology Group (COG) and the Erwinaze Master Treatment Protocol (EMTP). The COG and EMTP have contributed to the refinement and optimization of ASNase therapy for acute lymphoblastic leukemia. Overall, the milestones in the development of ASNase for acute lymphoblastic leukemia treatment highlight the progress made in understanding the unique pharmacokinetic properties of different ASNase preparations and tailoring treatment protocols accordingly. The approval of pegylated E. coli ASNase and ASNase Erwinia chrysantemi has expanded

1176-655: The College de France and at the Jardin des Plantes , member of the Council of Industry and Commerce, commissioner on the pharmacy laws, and finally professor of chemistry to the Medical Faculty, to which he succeeded on Fourcroy's death in 1809. His lectures, which were supplemented with practical laboratory teaching, were attended by many chemists who subsequently attained distinction. A lesser-known contribution and finding of his included

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1232-549: The European Union, asparaginase (Enrylaze) is indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma. The most common use of asparaginases is as a processing aid in the manufacture of food. Asparaginases are used as a food processing aid to reduce the formation of acrylamide , a suspected carcinogen , in starchy food products such as snacks, biscuits and fried potato. The main side effect

1288-500: The FDA approved asparaginase erwinia chrysanthemi (recombinant)-rywn) as a component of a multi-agent chemotherapeutic regimen for the treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma in people aged one month or older who have developed hypersensitivity to E. coli -derived asparaginase. The FDA granted the application for asparaginase erwinia chrysanthemi (recombinant)-rywn fast track and orphan drug designations. In

1344-422: The FDA approved calaspargase pegol-mknl, an asparagine specific enzyme, as a component of a multi-agent chemotherapeutic regimen for acute lymphoblastic leukemia in pediatric and young adult patients age 1 month to 21 years. This new product provides for a longer interval between doses compared to other available pegaspargase products. Calaspargase pegol-mknl has received FDA orphan drug designation. In June 2021,

1400-527: The FDA considered the observed and simulated data as sufficient evidence to fulfill the required efficacy target, forming the basis for their decision. Significantly, JZP-458 offers a solution to one of the prominent challenges in patient care for individuals with acute lymphoblastic leukemia/lymphoblastic lymphoma, which is the scarcity of reliable drugs. Its dependable manufacturing process, along with its proven efficacy and safety showcased in AALL1931, makes JZP-458

1456-507: The German chemist Hermann Kolbe showed that this surmise was wrong; instead, Kolbe concluded that asparagine was an amide of an amine of succinic acid . In 1886, the Italian chemist Arnaldo Piutti (1857–1928) discovered a mirror image or " enantiomer " of the natural form of asparagine, which shared many of asparagine's properties, but which also differed from it. Since the structure of asparagine

1512-476: The Maillard reaction. By adding asparaginase before baking or frying the food, asparagine is converted into another common amino acid, aspartic acid , and ammonium . 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

1568-503: The US Food and Drug Administration (FDA) granted approval to pegaspargase for the first-line treatment of people with acute lymphoblastic leukemia as a component of a multiagent chemotherapy regimen. Pegaspargase was previously approved in February 1994 for the treatment of patients with acute lymphoblastic leukemia who were hypersensitive to native forms of L-asparaginase. In December 2018,

1624-500: The United States for the treatment of acute lymphoblastic leukemia. As researchers developed deeper into ASNase treatment protocols, it became evident that different preparations of the enzyme exhibited distinct pharmacokinetic properties, necessitating tailored dosing schedules. This realization prompted further clinical trials to characterize outcomes under various ASNase treatment regimens. Subsequently, pegylated E . coli ASNase

1680-399: The achievement and maintenance of nadir serum asparaginase activity (NSAA) above the level of 0.1 U/mL.  The results of modeling and simulations showed that for a dosage of 25 mg/m2 administered intramuscularly every 48 hours, the proportion of patients maintaining NSAA ≥ 0.1 U/mL at 48 hours after a dose of Rylaze was 93.6% (95% CI= 92.6%-94.6%). The safety evaluation of JZP-458 in

1736-481: The element from the oxide. At first his work appeared as that of his master and patron Fourcroy, then in their joint names; in 1790 he began to publish on his own, and between that year and 1833 his name is associated with 376 papers. Most of these were simple records of patient and laborious analytical operations, and it is perhaps surprising that among all the substances he analysed he detected only two new elements, beryllium in 1798 in beryl and chromium in 1797 in

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1792-462: The exception of proline . Asparagine can be hydroxylated in the HIF1 hypoxia-inducible transcription factor . This modification inhibits HIF1-mediated gene activation. Asparagine is not essential for humans, which means that it can be synthesized from central metabolic pathway intermediates and is not required in the diet. Asparagine is found in: The precursor to asparagine is oxaloacetate , which

1848-406: The first hypersensitivity event was observed at a median time of 27 days after the initial administration of asparaginase (Erwinia chrysanthemi) (recombinant)-rywn, ranging from 1 to 171 days. Among the reported reactions, rash was the most frequently observed, occurring in 17% of patients. Notably, none of the patients experienced a severe rash. The median time from the first dose to the onset of rash

1904-416: The hydrogen bond interactions that would otherwise be satisfied by the polypeptide backbone. Asparagine also provides key sites for N-linked glycosylation , modification of the protein chain with the addition of carbohydrate chains. Typically, a carbohydrate tree can solely be added to an asparagine residue if the latter is flanked on the C side by X- serine or X- threonine , where X is any amino acid with

1960-471: The incidence of treatment-emergent AEs, particularly nausea, aligns with the expected side effect profile associated with asparaginase therapy. Nausea has been reported as a common adverse event in previous studies investigating asparaginase-based treatments. On the other hand, a study claimed that in clinical trials, approximately 25% of patients treated with asparaginase encountered hypersensitivity reactions, with 2% experiencing severe reactions. The onset of

2016-452: The initial treatment cycle with JZP-458, the percentage of patients reaching NSAA levels of at least 0.1 IU/mL within 72 hours was found to be 64% (95% CI=47%-82%) in cohort 1a, 91% (95% CI=84%-97%) in cohort 1b, and 90% (95% CI=81%-98%) in cohort 1c. Within 48 hours, over 95% of patients in each cohort achieved NSAA levels of at least 0.1 IU/mL. Specifically, in cohort 1a, 97% of patients (95% CI=91%-100%) achieved this level, while in cohort 1b,

2072-468: The percentage was 99% (95% CI=96%-100%), and in cohort 1c, it was 96% (95% CI=90%-100%). These findings indicate that the majority of patients across all cohorts achieved the desired NSAA levels within 48 to 72 hours of JZP-458 treatment initiation. A study was carried out to investigate the safety and efficacy related to JZP-458 phase II and III treatment. Out of the total patients (n= 167), 124 individuals (74.3%) experienced adverse events (AEs) related to

2128-409: The phase I clinical trial demonstrated a safety profile comparable to that of other asparaginases. Across all administered dose levels (25 mg/m for the i.m. route of administration and 37.5 mg/m for the i.v. route), JZP-458 exhibited favorable tolerability without any unexpected adverse events (AEs), serious AEs, or AEs of grade 3 or higher. Among the treatment-emergent AEs reported, nausea

2184-431: The same year, the German chemist Justus Liebig provided a more accurate formula. In 1846 the Italian chemist Raffaele Piria treated asparagine with nitrous acid , which removed the molecule's amine (–NH 2 ) groups and transformed asparagine into malic acid . This revealed the molecule's fundamental structure: a chain of four carbon atoms. Piria thought that asparagine was a diamide of malic acid; however, in 1862

2240-614: The study of hens fed a known amount of mineral. "Having calculated all the lime in oats fed to a hen, found still more in the shells of its eggs. Therefore, there is a creation of matter. In what way, no one knows." From 1809 he was professor at the University of Paris . He was elected a member of the American Philosophical Society in 1811 and a foreign member of the Royal Swedish Academy of Sciences in 1816. He

2296-430: The therapeutic options available for acute lymphoblastic leukemia patients. Ongoing research and clinical trials continue to advance our knowledge and improve outcomes in the treatment of this challenging disease. Numerous clinical studies have been conducted to evaluate the efficacy and safety of Erwinase in the treatment of acute lymphoblastic leukemia. One of the primary concerns in acute lymphoblastic leukemia treatment

Asparagine - Misplaced Pages Continue

2352-475: The treatment of acute lymphoblastic leukemia and lymphoblastic lymphoma are abnormal liver tests, nausea, muscle and bone pain, and fatigue. Asparaginase was approved for medical use in the United States in 1978. It is on the World Health Organization's List of Essential Medicines . It is often made from Escherichia coli ( E. coli ) or Erwinia chrysanthemi . The development of JZP-458 as

2408-423: The treatment of acute lymphoblastic leukemia. While adverse events may occur, proper monitoring and management strategies can effectively address these challenges. Further research is needed to better understand the long-term efficacy and safety outcomes of Erwinase, particularly in comparison to other asparaginase formulations. Continued investigation and refinement of treatment protocols will contribute to maximizing

2464-590: The treatment, and among them, 86 patients (51.5%) encountered grade 3 or 4 treatment-related AEs. The most prevalent nonhematologic grade 3 or 4 treatment-related AEs included febrile neutropenia (9.0%), elevated levels of alanine aminotransferase (7.8%), and nausea (5.4%). The authors have also claimed that in total, 21 patients (12.6%) discontinued the use of JZP-458 due to treatment-related AEs. The reasons for discontinuation were pancreatitis (6.0%), allergic reactions (5.4%), including anaphylaxis (1.8%), increased alanine aminotransferase (0.6%), and hyperammonemia (0.6%). It

2520-410: Was 33.5 days, with a range of 1 to 127 days. These results provide valuable insights into the safety of JZP-458 and support its potential as a well-tolerated treatment option for the targeted indication. Further investigations, including larger-scale clinical trials, are warranted to confirm these findings and assess the overall efficacy and safety of JZP-458 in a broader patient population. Efficacy

2576-570: Was a French pharmacist and chemist . He was the discoverer of chromium and beryllium . Vauquelin was born at Saint-André-d'Hébertot in Normandy , France, the son of Nicolas Vauquelin, an estate manager, and his wife, Catherine Le Charterier. His first acquaintance with chemistry was gained as laboratory assistant to an apothecary in Rouen (1777–1779), and after various vicissitudes he obtained an introduction to A. F. Fourcroy , in whose laboratory he

2632-549: Was administered at various dosages and routes, and the results were used to develop a model to predict serum asparaginase activity at various timepoints. The FDA approval of asparaginase erwinia chrysanthemi (recombinant) (Rylaze) was based on evidence from one ongoing clinical trial (NCT04145531) in 102 children and adult participants with a type of cancer called acute lymphoblastic leukemia/lymphoblastic lymphoma. These participants had developed allergy to another type of asparaginase (E.coli based long acting asparaginase). The trial

2688-670: Was an assistant from 1783 to 1791. Moving to Paris, he became a laboratory assistant at the Jardin du Roi and was befriended by a professor of chemistry. In 1791 he was made a member of the Academy of Sciences and from that time he helped to edit the journal Annales de Chimie (Chemical annals) , although he left the country for a while during the height of the French Revolution . In 1798 Vauquelin discovered beryllium oxide by extracting it from an emerald (a beryl variety); Klaproth isolated

2744-484: Was approved in 1994 as a second-line treatment and later in 2006 as a first-line treatment for acute lymphoblastic leukemia. Another ASNase variant, ASNase Erwinia chrysantemi, obtained authorization for use in the United Kingdom in 1985, and gained approval from the US Food and Drug Administration in 2011. These developments have significantly influenced treatment strategies and protocols, as evidenced by initiatives such as

2800-507: Was conducted in 67 sites across the United States and Canada. Normal asparaginase costs less than its pegylated version, pegaspargase . However, because it doesn't stay as long in the body, the injections need to be more frequent, with the result that total cost of treatment may be lower for the pegylated version. Crisantaspase is the British Approved Name (BAN) for asparaginase obtained from Erwinia chrysanthemi . Colaspase

2856-463: Was elected to the Chamber of Deputies in 1828. In 1806, working with asparagus , he and Pierre Jean Robiquet (future discoverer of the famous red dye alizarin , then a young chemist and his assistant) isolated the amino acid asparagine , the first one to be discovered. He also discovered pectin and malic acid in apples , and isolated camphoric acid and quinic acid . His death occurred while he

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2912-473: Was evaluated in Study JZP458-201 (NCT04145531), an open-label, multi-cohort, multicenter trial in 102 patients with acute lymphoblastic leukemia or lymphoblastic lymphoma with hypersensitivity to E. coli -derived asparaginase as a component of a multi-agent chemotherapeutic regimen. The median age was 10 years with a range of 1 to 24 years. Patients received Rylaze intramuscularly at various dosages. After

2968-672: Was found out that it is not the serum itself which provoke the tumour regression, but rather the enzyme asparaginase. After researchers comparing different kinds of asparaginases, the one derived from Escherichia coli and Erwinia chrysanthemi turned out to have the best anti-cancer ability. E. coli has thereby become the main source of asparaginase due to the factor that it is also easy to produce in large amount. The pharmacokinetics of asparaginase erwinia chrysanthemi (recombinant) (Rylaze) were evaluated in 225 recipients in study JZP458-201 (NCT04145531), an open-label multicenter trial in which asparaginase erwinia chrysanthemi (recombinant)

3024-491: Was on a visit to his birthplace. Among his best known works is "Manuel de l'essayeur" (Manual of the assayer). The plant genus Vauquelinia is named in his honour, as is the Vauquelin , a white of egg foam associated with molecular gastronomy , and the mineral vauquelinite , discovered at the same mine as the crocoite from which Vauquelin isolated chromium. [REDACTED]   This article incorporates text from

3080-489: Was still not fully known – the location of the amine group within the molecule was still not settled – Piutti synthesized asparagine and thus published its true structure in 1888. Since the asparagine side-chain can form hydrogen bond interactions with the peptide backbone, asparagine residues are often found near the beginning of alpha-helices as asx turns and asx motifs , and in similar turn motifs, or as amide rings , in beta sheets . Its role can be thought as "capping"

3136-495: Was the most frequently observed in two or more healthy volunteers within each dosing cohort. A further study has examined the incidence and severity of AEs in a cohort of 199 patients with acute lymphoblastic leukemia and treated with Erwinase. The study found that the most common AEs were allergic reactions, pancreatitis, hepatotoxicity, and coagulation disorders. However, the majority of these AEs were manageable with appropriate monitoring and intervention strategies. Furthermore,

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