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 - Funding Information:
This study was supported by the grants from National Institute of Health (P41EB015908, RO1CA154843), Cancer Prevention Research Institute of Texas (RP140021-P2), the Donna and Kenneth R. Peak Foundation, The Kenneth R. Peak Brain and Pituitary Tumor Treatment Center at Houston Methodist Hospital, The Taub Foundation, The John S. Dunn Foundation, The Blanche Green Estate Fund of the Pauline Sterne Wolff Memorial Foundation, The Verelan Foundation, The Houston Methodist Hospital Foundation, The American Brain Tumor Association, and by many brave patients and families who have been impacted by the devastating effects of brain cancers and central nervous system disease.
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
UR - https://www.scopus.com/pages/publications/85032282944
UR - https://www.scopus.com/inward/citedby.url?scp=85032282944&partnerID=8YFLogxK
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 -