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Real‐time assessment of Krebs cycle metabolism using hyperpolarized C magnetic resonance spectroscopy
Author(s) -
Schroeder Marie A.,
Atherton Helen J.,
Ball Daniel R.,
Cole Mark A.,
Heather Lisa C.,
Griffin Julian L.,
Clarke Kieran,
Radda George K.,
Tyler Damian J.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.09-129171
Subject(s) - citric acid cycle , glutamate receptor , chemistry , flux (metallurgy) , tricarboxylic acid , metabolism , nuclear magnetic resonance spectroscopy , nuclear magnetic resonance , glycolysis , medicine , endocrinology , biochemistry , biophysics , biology , physics , receptor , organic chemistry
The Krebs cycle plays a fundamental role in cardiac energy production and is often implicated in the energetic imbalance characteristic of heart disease. In this study, we measured Krebs cycle flux in real time in perfused rat hearts using hyperpolarized magnetic resonance spectroscopy (MRS). [2‐ 13 C]Pyru‐ vate was hyperpolarized and infused into isolated perfused hearts in both healthy and postischemic metabolic states. We followed the enzymatic conversion of pyruvate to lactate, acetylcarnitine, citrate, and glutamate with 1 s temporal resolution. The appearance of 13 C‐labeled glutamate was delayed compared with that of other metabolites, indicating that Krebs cycle flux can be measured directly. The production of 13 C‐ labeled citrate and glutamate was decreased postischemia, as opposed to lactate, which was significantly elevated. These results showed that the control and fluxes of the Krebs cycle in heart disease can be studied using hyperpolarized [2‐ 13 C]pyruvate.— Schroeder, M. A., Atherton, H. J., Ball, D. R., Cole, M. A., Heather, L. C., Griffin, J. L., Clarke, K., Radda, G. K., Tyler, D. J. Real‐time assessment of Krebs cycle metabolism using hyperpolarized 13C magnetic resonance spectroscopy. FASEBJ. 23, 2529–2538 (2009)