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

Kumar Pichumani, Tomoyuki Mashimo, Vamsidhara Vemireddy, Omkar B. Ijare, Bruce E. Mickey, Craig R. Malloy, Isaac Marin-Valencia, David S. Baskin, Robert M. Bachoo, Elizabeth A. Maher

Research output: Contribution to journalLetter

3 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)3548-3554
Number of pages7
JournalFEBS Letters
Volume591
Issue number21
DOIs
StatePublished - Nov 1 2017

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Keywords

  • C isotopomer
  • acetyl-CoA
  • glutamate and glutamine synthesis
  • peripheral metabolism
  • [1,2-C]acetate

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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