title: Metabolism of hyperpolarized [1-(13)C]pyruvate through alternate pathways in rat liver.
abstract: The source of hyperpolarized (HP) [(13)C]bicarbonate in the liver during metabolism of HP [1-(13)C]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 [(13)C]bicarbonate during metabolism of HP [1-(13)C]pyruvate by the liver in rats after 21 h of fasting compared to rats with free access to food. The (13)C NMR of HP [(13)C]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-(13)C]pyruvate. (13)C 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 [(13)C]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 [(13)C]bicarbonate exclusively reflects decarboxylation of HP [1-(13)C]pyruvate via pyruvate dehydrogenase.
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.|Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Eunsook S
authors.initials: ES
authors.lastname: Jin
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Karlos X
authors.initials: KX
authors.lastname: Moreno
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.|Radiology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Jian-Xiong
authors.initials: JX
authors.lastname: Wang
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Leila
authors.initials: L
authors.lastname: Fidelino
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.|Radiology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Merritt
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.|Radiology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.|Department of Chemistry, University of Texas at Dallas, Richardson, TX, 75080, USA.
authors.forename: A Dean
authors.initials: AD
authors.lastname: Sherry
authors.affiliation: Advanced Imaging Research Center, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.|Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.|Radiology, University of Texas Southwestern Medical Center, Dallas, TX, 75390, USA.|VA North Texas Health Care System, Dallas, TX, 75216, USA.
authors.forename: Craig R
authors.initials: CR
authors.lastname: Malloy
mesh_terms: D000409:Alanine / Q000378:metabolism; D000818:Animals; D001639:Bicarbonates / Q000378:metabolism; D002247:Carbon Isotopes; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D002952:Citric Acid Cycle; D005943:Gluconeogenesis; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy / Q000379:methods*; D019764:Phosphoenolpyruvate Carboxykinase (ATP); D066244:Proton Magnetic Resonance Spectroscopy; D011766:Pyruvate Carboxylase / Q000378:metabolism; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D019289:Pyruvic Acid / Q000378:metabolism*; D017207:Rats, Sprague-Dawley
chemical_list: D001639:Bicarbonates; D002247:Carbon Isotopes; D011768:Pyruvate Dehydrogenase Complex; D019344:Lactic Acid; D019289:Pyruvic Acid; D019764:Phosphoenolpyruvate Carboxykinase (ATP); D011766:Pyruvate Carboxylase; D000409:Alanine
keywords: NMR; bicarbonate; gluconeogenesis; glutamate; hyperpolarization; phosphoenolpyruvate carboxykinase; pyruvate carboxylase; pyruvate dehydrogenase
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