Hepatic gluconeogenesis influences (13)C enrichment in lactate in human brain tumors during metabolism of [1,2-(13)C]acetate

Neurochem Int. 2016 Jul:97:133-6. doi: 10.1016/j.neuint.2016.03.015. Epub 2016 Mar 26.

Abstract

(13)C-enriched compounds are readily metabolized in human malignancies. Fragments of the tumor, acquired by biopsy or surgical resection, may be acid-extracted and (13)C NMR spectroscopy of metabolites such as glutamate, glutamine, 2-hydroxyglutarate, lactate and others provide a rich source of information about tumor metabolism in situ. Recently we observed (13)C-(13)C spin-spin coupling in (13)C NMR spectra of lactate in brain tumors removed from patients who were infused with [1,2-(13)C]acetate prior to the surgery. We found, in four patients, that infusion of (13)C-enriched acetate was associated with synthesis of (13)C-enriched glucose, detectable in plasma. (13)C labeled glucose derived from [1,2-(13)C]acetate metabolism in the liver and the brain pyruvate recycling in the tumor together lead to the production of the (13)C labeled lactate pool in the brain tumor. Their combined contribution to acetate metabolism in the brain tumors was less than 4.0%, significantly lower than the direct oxidation of acetate in the citric acid cycle in tumors.

Keywords: Brain metastases; Glioblastoma; Isotopomers; Metabolism; Pyruvate recycling; [1,2-(13)C]acetate.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetates / metabolism*
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Carbon Isotopes / metabolism*
  • Gluconeogenesis / physiology*
  • Humans
  • Lactic Acid / metabolism*
  • Liver / metabolism*
  • Magnetic Resonance Spectroscopy / methods

Substances

  • Acetates
  • Carbon Isotopes
  • Lactic Acid