Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/23/2003
Publication Date: 12/1/2003
Citation: Cohen, D.M., Guthrie, P.H., Gao, X., Sakai, R., Taegtmeyer, H. 2003. Glutamine cycling in isolated working rat heart. American Journal of Physiology - Endocrinology and Metabolism. 285(6):E1312-E1316.
Interpretive Summary: We studied the metabolism of rat hearts, using nuclear magnetic resonance spectroscopy (NMR), which allowed us to observe that a particular chemical was being formed in the heart. The observation of the synthesis of this chemical (glutamine) is important because it might serve as an energy reservoir for the heart, and hence (in the future) might serve as a focus of treatment of heart failure. More studies are underway to explore the role of this chemical in the metabolism of the heart.
Technical Abstract: To what extent does glutamine turnover keep pace with oxidative metabolism in the rat heart? To address this question, the following substrates were presented to the isolated, working rat heart: (1) glucose (5 mM), insulin (40 mU/ml) and [2-13C]acetate (5mM) (high workload, n= 5); (2) pyruvate (2.5 mM) and [2-13C]acetate (5 mM) (normal workload, n= 5); or (3) propionate(1 mM) and [2-13C]acetate (2.5mM) (normal workload, n=3). In a subset of these experiments the exchange of glutamate and glutamine was quantified by separation with ion exchange chromatography and analysis by gas chromatography-mass spectrometry. There was an apparent equilibration of mass isotopomers of glutamate and glutamine after 50 minutes of perfusion. The fractional enrichment in glutamine was 31% of the enrichment of glutamate with the three different perfusates. From high resolution NMR spectra, we found a ratio of glutamine to glutamate content of 94.1%, 53.4% and 96.9%, respectively, for each experimental group. We conclude that, in the working heart, glutamine and glutamate are in isotopic equilibrium, consistent with an energy-consuming substrate cycle.