Metabolism of hyperpolarized [1-13C]pyruvate through alternate pathways in rat liver

Eunsook S. Jin, Karlos X. Moreno, Jian Xiong Wang, Leila Fidelino, Matthew E. Merritt, A. Dean Sherry, Craig R. Malloy

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

The source of hyperpolarized (HP) [13C]bicarbonate in the liver during metabolism of HP [1-13C]pyruvate is uncertain and likely changes with physiology. Multiple processes including decarboxylation through pyruvate dehydrogenase or pyruvate carboxylase followed by subsequent decarboxylation via phosphoenolpyruvate carboxykinase (gluconeogenesis) could play a role. Here we tested which metabolic fate of pyruvate contributed to the appearance of HP [13C]bicarbonate during metabolism of HP [1-13C]pyruvate by the liver in rats after 21h of fasting compared to rats with free access to food. The 13C NMR of HP [13C]bicarbonate was observed in the liver of fed rats, but not in fasted rats where pyruvate carboxylation and gluconeogenesis was active. To further explore the relative fluxes through pyruvate carboxylase versus pyruvate dehydrogenase in the liver under typical conditions of hyperpolarization studies, separate parallel experiments were performed with rats given non-hyperpolarized [2,3-13C]pyruvate. 13C NMR analysis of glutamate isolated from the liver of rats revealed that flux from injected pyruvate through pyruvate dehydrogenase was dominant under fed conditions whereas flux through pyruvate carboxylase dominated under fasted conditions. The NMR signal of HP [13C]bicarbonate does not parallel pyruvate carboxylase activity followed by subsequent decarboxylation reaction leading to glucose production. In the liver of healthy well-fed rats, the appearance of HP [13C]bicarbonate exclusively reflects decarboxylation of HP [1-13C]pyruvate via pyruvate dehydrogenase.

Original languageEnglish (US)
Pages (from-to)466-474
Number of pages9
JournalNMR in biomedicine
Volume29
Issue number4
DOIs
StatePublished - Apr 1 2016

Keywords

  • Bicarbonate
  • Gluconeogenesis
  • Glutamate
  • Hyperpolarization
  • NMR
  • Phosphoenolpyruvate carboxykinase
  • Pyruvate carboxylase
  • Pyruvate dehydrogenase

ASJC Scopus subject areas

  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging
  • Spectroscopy

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