Measurement of ¹³C turnover into glutamate and glutamine pools in brain tumor patients

Malignant brain tumors are known to utilize acetate as an alternate carbon source in the citric acid cycle for their bioenergetics. ¹³C NMR-based isotopomer analysis has been used to measure turnover of ¹³C-acetate carbons into glutamate and glutamine pools in tumors. Plasma from the patients infused with [1,2-¹³C]acetate further revealed the presence of ¹³C isotopomers of glutamine, glucose, and lactate in the circulation that were generated due to metabolism of [1,2-¹³C]acetate by peripheral organs. In the tumor cells, [4-¹³C] and [3,4-¹³C]glutamate and glutamine isotopomers were generated from blood-borne ¹³C-labeled glucose and lactate which were formed due to [1,2-¹³C[acetate metabolism of peripheral tissues. [4,5-¹³C] and [3,4,5-¹³C]glutamate and glutamine isotopomers were produced from [1,2-¹³C]acetyl-CoA that was derived from direct oxidation of [1,2-¹³C] acetate in the tumor. Major portion of C4 ¹³C fractional enrichment of glutamate (93.3 ± 0.02%) and glutamine (90.9 ± 0.03%) were derived from [1,2-¹³C]acetate-derived acetyl-CoA.