Asparagine health benefit

Asparagine is one of the 20 most common natural amino acids on Earth. It has carboxamide as the side chain's functional group. A reaction between asparagine and reducing sugars or reactive carbonyls produces acrylamide (acrylic amide) in food when heated to sufficient temperature. These products occur in baked goods such as French fries, potato chips, and roasted coffee.
   L-asparagine is an endogenous amino acid necessary for the function of some neoplastic cells, such as lymphoblasts.

Potentially toxic acrylamide is largely derived from heat-induced reactions between the amino group of the free amino acid asparagine and carbonyl groups of glucose and fructose in cereals, potatoes, and other plant-derived foods.

Use of L-asparaginase in acute lymphoblastic leukemia: recommendations of the Polish Adult Leukemia Group.
Pol Arch Med Wewn. 2008 Nov; Piatkowska-Jakubas B, Krawczyk-Kuliś M, Giebel S, Adamczyk-Cioch M, Czyz A, Lech Marańda E, Paluszewska M, Pałynyczko G, Piszcz J, Hołowiecki J; Polish Adult Leukemia Group. Department of Hematology, Jagiellonian University, Medical College, Kraków, Poland.
L-asparaginase is a hydrolase that catalyzes the conversion of L-asparagine--an endogenous amino acid necessary for the function of some neoplastic cells, such as lymphoblasts. In most human cells deficiency of L-asparagine can be compensated by alternative synthesis pathway through which L-asparagine is produced from aspartic acid and glutamine by asparagine synthethase. Depletion of L-asparagine from plasma by L-asparaginase results in inhibition of RNA and DNA synthesis with the subsequent blastic cell apoptosis. Owing to the unique anti-cancer mechanism of action, L-asparaginase has been introduced to the multi drug chemotherapy in children and adults with acute lymphoblastic leukemia, which has contributed to significant improvement of therapy outcomes and to achieve complete remission in about 90% of patients. Notwithstanding its high therapeutic efficacy, L-asparaginase can increase the risk of thrombosis. Inhibition of protein synthesis causes most complications observed during treatment with a native and pegylated form of L-asparaginase, including impaired functions of liver, kidneys or central nervous system. Thrombotic events occur as a result of inhibited synthesis of anticoagulant proteins (mainly antithrombin). Coagulopathy has been observed in 1-4% of patients treated with the pegylated L-asparaginase and in 2-15% of those receiving its native form. In this paper approaches to optimize the therapy with L-asparaginase have been discussed.

Is asparaginase a critical component in the treatment of acute lymphoblastic leukemia?
Best Pract Res Clin Haematol. 2008 Dec; Douer D. USC/Norris Cancer Center, 1441 Eastlake Ave Rm 3460, Los Angeles, CA 90033, United States.
The outcome of pediatric acute lymphoblastic leukemia (ALL) has improved dramatically over the last 40 years through a systematic approach of well-designed large trials including use of asparaginase. Although asparaginase has been incorporated with other drugs in adult ALL protocols, it has been associated with more toxicities in older patients resulting in caution in the inclusion of asparaginase-containing regimens for adults. Consequently, to date, no randomized trials with asparaginase have been performed in adults. Furthermore, adult regimens that do not include asparaginase have shown comparable outcomes to regimens with asparaginase, which makes the necessity of asparaginase in adult regimens unclear. There are several other factors which influence the role of asparaginase use in adults, including the level and sustainability of asparagine depletion, schedule, dosing, and form of asparaginase and the consequent toxicities and immunogenicity reactions.

Identification and characterization of asparagine deamidation in the light chain CDR1 of a humanized IgG1 antibody.
Anal Biochem. 2009 Sep 15; Vlasak J, Bussat MC, Wang S, Wagner-Rousset E, Schaefer M, Klinguer-Hamour C, Kirchmeier M, Corvaïa N, Ionescu R, Beck A.
Merck & Co. Inc, West Point, PA, USA.
Despite technological advances, detection of deamidation in large proteins remains a challenge and the use of orthogonal methods is needed for unequivocal assignment. By a combination of cation-exchange separation, papain digestion, and a panel of mass spectrometry techniques we identified asparagine deamidation in light chain complementarity determining region 1 (CDR1) of a humanized IgG1 monoclonal antibody. The reaction yields both Asp and isoAsp, which were assigned by Edman degradation and by isoAsp detection using protein isoaspartate methyltransferase. The deamidated antibody variants were less potent in antigen binding compared to the nondegraded antibody. Changes in near-UV CD spectra, susceptibility to papain cleavage in an adjacent CDR2 loop, and the tendency of the newly formed isoAsp to undergo isomerization suggest local perturbations in the structure of the isoAsp-containing antibody.