L-Asparagine

L-Asparagine is an essential amino acid for leukemic cells and a substrate for L-Asparaginase. L-Asparaginase is a potent anti-leukemic enzyme that promotes asparagine (Asn) and glutamine (Gln) depletion and inhibits protein biosynthesis in lymphoblasts. Removal of L-asparagine from plasma by L-Asparaginase results in inhibition of RNA and DNA synthesis and subsequent apoptosis. L-Asparaginase has cell-killing ability in vitro and in vivo, and selectively inhibits the growth of cancer cells with low asparagine synthetase (AASNS) expression. L-Asparagine can be used as a biomarker and sensor for the study of childhood acute lymphoblastic leukemia^{[1][2][3][4][5]}. In Vitro: L-Asparagine is the biological substrate of L-Asparaginase. The potential side effects of L-Asparaginase are causing normal cell death and inducing inflammation, metabolic disorders and neurotoxicity after use. The toxic side effects of L-Asparaginase may be caused by the action of glutaminase in it^[1].
L-Asparagine and L-Asparaginase have also been used to develop biosensors for analyzing asparagine levels in leukemia or food industry. In application, the characteristics of L-Asparagine hydrolysis, which produces ammonium ions and causes pH changes, can be used to determine the level of L-Asparagine by color and absorbance changes^[1].
L-Asparaginase can preferentially kill leukemia cells, and the leukemia cell killing rate can be accurately measured using leukemia cell surface markers. L-Asparaginase showed no significant dose response at doses of 0.0001-0.1 IU/mL^[2].
In Vivo: L-Asparagine is widely found in bacteria, fungi, actinomycetes, plants and animals. L-Asparagine from Escherichia coli (E. coli) and Enterobacter chrysanthemi (E. chrysanthemi) has been used to acute lymphoblastic leukemia (ALL) research, and has made progress in the subcutaneous Gardner 6C3HED lymphosarcoma model established in mice^[1].
In the NOD.Cg-PRKDC^scidIL2RG^tm1Wjl (NSG) mouse model, L-Asparaginase (1000 or 5000 IU/kg; intraperitoneal injection; once a day for 3 consecutive days) significantly depletes L-Asparagine in the blood; in the high-dose group, L-Asparagine also recoveres slowly after the cessation of L-Asparaginase injection^[3].
When L-Asparaginase is encapsulated in red blood cells (ASP-RBC) and given to Swiss mice by intravenous injection (200 or 1000 IU/kg), the depletion time of L-Asparagine in their plasma is prolonged. In the 1000 IU/kg dose group, levels of L-Asparagine remains undetectable for up to 14 days, and the half-life of the enzyme is 9-10 days^[4].