Asparaginase derived from _Escherichia coli_ (L-asparagine amidohydrolase, EC 3.five.1.1) is an enzyme answerable for the metabolism of L-asparagine, through catalyzing L-asparagine into L-aspartic acid and ammonia. It additionally allows the manufacturing of oxaloacetate which is wanted for widespread cell metabolism. Asparaginase from _E. coli_ has clinically proven to showcase antitumor actions in models of leukaemias [A31996, A31997]. L-asparaginase of _E. coli_ is advertised below numerous one-of-a-kind exchange names, consisting of Elspar, for the remedy of acute lymphoblastic leukemia (ALL) as part of a multi-agent chemotherapeutic routine. it's far to be had as intramuscular or intravenous injections. therapeutic L-asparaginase from _E. coli_ works through depleting the degrees of non-vital amino acid, asparagine, in lymphoblastic leukemic cells as a result promoting apoptotic cellular loss of life [A31999]. For sufferers who develop hypersensitivity to _E. coli_-derived formulations of L-asparaginase, the usage of PEGylated or non-PEGylated [DB08886] is usually recommended [A31999].
In clinical trials of patients with previously untreated, standard-risk ALL, administration of asparaginase resulted in a decrease of plasma asparagine levels from average of 41 Î¼M to less than 3 Î¼M [FDA Label]. The native asparaginase in whom plasma enzyme activity before treatment was greater than 0.1 International Units/mL [FDA Label]. In this study, cerebrospinal fluid asparagine levels in patients treated with asparaginase decreased from 2.8 Î¼M (pretreatment) to 1.0 Î¼M and 0.3 Î¼M at day 7 and day 28 of induction, respectively [FDA Label]. Native E. coli asparaginase results in asparagine depletion in 14 to 23 days following administration [A31999].
Indicated as a component of a multi-agent chemotherapeutic regimen for the treatment of patients with acute lymphoblastic leukemia (ALL) [FDA Label].
Asparagine is a non-essential amino acid that maintains DNA, RNA and protein synthesis and promotes cell growth. While healthy and normal cells are capable of obtaining asparagine via dietary intake or synthesizing the asparagine from aspartate via asparagine synthetase activity, lymphoblastic leukemic cells lack the asparagine synthetase enzyme and cannot produce asparagine _de novo_ [A31999]. Thus, leukemic cells rely on exogenous source of asparagine for protein synthesis and cell survival [A31999]. L-asparagine from E. coli serves to deplete plasma levels of asparagine in leukemic cells by converting L-asparagine to L-aspartic acid and ammonia [A31999], leading to reduced reduced DNA, RNA and protein synthesis; inhibition of cell growth; and ultimately the activation of apoptotic cell-death mechanisms [A31999]. Normal cells, however, are able to synthesize asparagine and thus are affected less by the rapid depletion produced by treatment with the enzyme asparaginase [FDA Label].