TY - JOUR
T1 - Measurement of 13C turnover into glutamate and glutamine pools in brain tumor patients
AU - Pichumani, Kumar
AU - Mashimo, Tomoyuki
AU - Vemireddy, Vamsidhara
AU - Ijare, Omkar B.
AU - Mickey, Bruce E.
AU - Malloy, Craig R.
AU - Marin-Valencia, Isaac
AU - Baskin, David S.
AU - Bachoo, Robert M.
AU - Maher, Elizabeth A.
N1 - Publisher Copyright:
© 2017 Federation of European Biochemical Societies.
PY - 2017/11
Y1 - 2017/11
N2 - 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.
AB - 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.
KW - C isotopomer
KW - [1,2-C]acetate
KW - acetyl-CoA
KW - glutamate and glutamine synthesis
KW - peripheral metabolism
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U2 - 10.1002/1873-3468.12867
DO - 10.1002/1873-3468.12867
M3 - Article
C2 - 28963851
AN - SCOPUS:85032282944
SN - 0014-5793
VL - 591
SP - 3548
EP - 3554
JO - FEBS Letters
JF - FEBS Letters
IS - 21
ER -