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Metabolism of hyperpolarized [1‐ 13 C]pyruvate through alternate pathways in rat liver
Author(s) -
Jin Eunsook S.,
Moreno Karlos X.,
Wang JianXiong,
Fidelino Leila,
Merritt Matthew E.,
Sherry A. Dean,
Malloy Craig R.
Publication year - 2016
Publication title -
nmr in biomedicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.278
H-Index - 114
eISSN - 1099-1492
pISSN - 0952-3480
DOI - 10.1002/nbm.3479
Subject(s) - pyruvate carboxylase , pyruvate dehydrogenase complex , gluconeogenesis , pyruvate decarboxylation , pyruvate dehydrogenase phosphatase , pyruvate dehydrogenase kinase , decarboxylation , dihydrolipoyl transacetylase , biochemistry , chemistry , phosphoenolpyruvate carboxylase , bicarbonate , metabolism , endocrinology , medicine , biology , enzyme , catalysis
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. © 2016 The Authors. NMR in Biomedicine published by John Wiley & Sons Ltd.