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 Citations (Scopus)

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)
JournalNMR in Biomedicine
DOIs
StateAccepted/In press - 2016

Fingerprint

Pyruvic Acid
Metabolism
Liver
Rats
Pyruvate Carboxylase
Bicarbonates
Decarboxylation
Oxidoreductases
Gluconeogenesis
Nuclear magnetic resonance
Fluxes
Carboxylation
Phosphoenolpyruvate
Physiology
Glutamic Acid
Fasting
Glucose
Food

Keywords

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

ASJC Scopus subject areas

  • Spectroscopy
  • Molecular Medicine
  • Radiology Nuclear Medicine and imaging

Cite this

Metabolism of hyperpolarized [1-13C]pyruvate through alternate pathways in rat liver. / Jin, Eunsook S.; Moreno, Karlos X.; Wang, Jian Xiong; Fidelino, Leila; Merritt, Matthew E.; Sherry, A. Dean; Malloy, Craig R.

In: NMR in Biomedicine, 2016.

Research output: Contribution to journalArticle

@article{b391dd1e8aab4bb3bbc362f4460940bd,
title = "Metabolism of hyperpolarized [1-13C]pyruvate through alternate pathways in rat liver",
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.",
keywords = "Bicarbonate, Gluconeogenesis, Glutamate, Hyperpolarization, NMR, Phosphoenolpyruvate carboxykinase, Pyruvate carboxylase, Pyruvate dehydrogenase",
author = "Jin, {Eunsook S.} and Moreno, {Karlos X.} and Wang, {Jian Xiong} and Leila Fidelino and Merritt, {Matthew E.} and Sherry, {A. Dean} and Malloy, {Craig R.}",
year = "2016",
doi = "10.1002/nbm.3479",
language = "English (US)",
journal = "NMR in Biomedicine",
issn = "0952-3480",
publisher = "John Wiley and Sons Ltd",

}

TY - JOUR

T1 - Metabolism of hyperpolarized [1-13C]pyruvate through alternate pathways in rat liver

AU - Jin, Eunsook S.

AU - Moreno, Karlos X.

AU - Wang, Jian Xiong

AU - Fidelino, Leila

AU - Merritt, Matthew E.

AU - Sherry, A. Dean

AU - Malloy, Craig R.

PY - 2016

Y1 - 2016

N2 - 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.

AB - 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.

KW - Bicarbonate

KW - Gluconeogenesis

KW - Glutamate

KW - Hyperpolarization

KW - NMR

KW - Phosphoenolpyruvate carboxykinase

KW - Pyruvate carboxylase

KW - Pyruvate dehydrogenase

UR - http://www.scopus.com/inward/record.url?scp=84959050201&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84959050201&partnerID=8YFLogxK

U2 - 10.1002/nbm.3479

DO - 10.1002/nbm.3479

M3 - Article

C2 - 26836042

AN - SCOPUS:84976217108

JO - NMR in Biomedicine

JF - NMR in Biomedicine

SN - 0952-3480

ER -