Inhibition of glutaminolysis does not decrease plasma succinate levels in rats (n = 5) undergoing severe HS. (A) An overview of glutamine metabolism and inhibition of glutaminase by CB839. (B) Inhibition of glutaminolysis by administration of glutaminase inhibitor CB-839 in vivo promotes accumulation of plasma glutamine but not accumulation of plasma succinate. (C) The drug could be detected through MS only in the plasma from rats receiving its administration, confirming its systemic bioavailability after the treatment. Labeling scheme in panels B and C is based on the presence (+) or absence (−) of shock, DMSO (control for vehicle to the drug CB-839), and glutaminase inhibitor. Three columns are graphed per each group, indicating baseline, postshock, and end-of-shock values. However, plasma levels of succinate significantly correlated with mortality in rats (D), and only 1 shock rat receiving glutaminase inhibitor survived (supplemental Figure 3).