NYMC Faculty Publications
The Metabolic Importance of the Overlooked Asparaginase II Pathway
Author Type(s)
Faculty
DOI
10.1016/j.ab.2020.114084
Journal Title
Analytical Biochemistry
First Page
114084
Document Type
Article
Publication Date
5-1-2022
Department
Biochemistry and Molecular Biology
Abstract
The asparaginase II pathway consists of an asparagine transaminase [l-asparagine + α-keto acid ⇆ α-ketosuccinamate + l-amino acid] coupled to ω-amidase [α-ketosuccinamate + HO → oxaloacetate + NH]. The net reaction is: l-asparagine + α-keto acid + HO → oxaloacetate + l-amino acid + NH. Thus, in the presence of a suitable α-keto acid substrate, the asparaginase II pathway generates anaplerotic oxaloacetate at the expense of readily dispensable asparagine. Several studies have shown that the asparaginase II pathway is important in photorespiration in plants. However, since its discovery in rat tissues in the 1950s, this pathway has been almost completely ignored as a conduit for asparagine metabolism in mammals. Several mammalian transaminases can catalyze transamination of asparagine, one of which - alanine-glyoxylate aminotransferase type 1 (AGT1) - is important in glyoxylate metabolism. Glyoxylate is a precursor of oxalate which, in the form of its calcium salt, is a major contributor to the formation of kidney stones. Thus, transamination of glyoxylate with asparagine may be physiologically important for the removal of potentially toxic glyoxylate. Asparaginase has been the mainstay treatment for certain childhood leukemias. We suggest that an inhibitor of ω-amidase may potentiate the therapeutic benefits of asparaginase treatment.
Recommended Citation
Cooper, A. J., Dorai, T., Pinto, J. T., & Denton, T. T. (2022). The Metabolic Importance of the Overlooked Asparaginase II Pathway. Analytical Biochemistry, 644, 114084. https://doi.org/10.1016/j.ab.2020.114084