Possible Interaction: Asparaginase and Glutamine

“There was correlation between asparaginase enzymatic activity and depletion of asparagine or glutamine in serum.”

“While experimental introduction of cytosolic asparaginase could enhance the synthesis of glutamine and increase tricarboxylic acid cycle anaplerosis and the synthesis of nucleotide precursors, cytosolic asparaginase suppressed the growth and survival of cells in glutamine-depleted medium in vitro and severely compromised the in vivo growth of tumor xenografts.”

“The depletion of extracellular Gln by treatment with l-asparaginase , in addition to inhibiting Gln uptake via the knockdown of a Gln transporter, led to the inhibition of cell growth in OVC cells with low expression of GS (GSlow-OVC cells).”

“ L-asparaginase is an enzyme that causes hydrolysis of L-asparagine and L-glutamine , leading to its reduction and, ultimately, depletion in peripheral blood and bone marrow.”

“ L-asparaginase (L-asp) exacerbated growth inhibition induced by glutamine starvation and suppressed OXPHOS and proliferation of Evi1/MF9 both in vitro and in vivo; high sensitivity to L-asp was caused by low expression of asparagine synthetase (ASNS) and L-asp-induced suppression of glutamine metabolism.”

“In the lymphoid cell lines Jurkat and Jeco, deprivation of Gln but not Asn specifically suppressed cell growth and survival, and phenocopied the action of L‐ASNase.”

“The Gln in medium could be depleted by two L-Asp drugs with high concentration.”

“For this reason, glutamine reduction is also necessary for full anti-leukemic activity of asparaginase.”

“Therefore, deamination of Gln may enhance the antileukemic effect of ASNase.”

“A glutamine deprivation-dependent cell shrinkage with activation of the CD95-mediated pathway was also observed when asparaginase was added to the medium.”