Isotope tracers have played an important role in determining the fate of substrates through multiple biochemical pathways in intact tissue. Virtually all of these techniques rely upon measurement of relative specific activities or fractional enrichments in individual carbon positions, for example, in a given metabolic product. We-have recently developed a NMR technique which takes advantage of 13c-13c coupling between adjacent carbons in any metabolite to provide a substantially more comprehensive analysis of the fate of any metabolic label. The method has been termed """"""""isotopomer analysis"""""""" and is applicable under a wide variety of physiological conditions, including nonsteady-state (NSS). We now proposed to use the method to examine a variety of metabolic issues in intact animals including fatty acid utilization in an in vivo pig heart model during control and postischemic periods and fatty acid, glucose, lactate, and ketone body contributions to the acetyl-CoA pools in vivo rat heart, liver, and brain in control animals, fasted animals, and in an animal model which simulates heavy exercise. For those tissues which achieve a steadystate (SS) isotopic distribution (this can be tested by comparing results from a SS and NSS isotopomer analysis of the same NMR data), the anaplerotic flux through the citric acid cycle pools relative to TCA cycle flux and the labeling pattern of the anaplerotic substrate may also be evaluated. These studies should provide a more complete, quantitative picture of the metabolic fate of various labeled subtrates in tissue and help resolve some current controversies involving fatty acid utilization in the ischemic myocardium, the direct versus indirect pathway for glycogen synthesis from glucose, and alternate sources of energy for the brain. we also propose to use these same techniques to examine the mechanism of oxygen wasting in heart muscle exposed to fatty acids using a perfused, working heart model and to investigate the possible metabolic significance of substrate channeling in tissue mitochondria under various physiological conditions.

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National Heart, Lung, and Blood Institute (NHLBI)
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University of Texas-Dallas
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Mishkovsky, Mor; Anderson, Brian; Karlsson, Magnus et al. (2017) Measuring glucose cerebral metabolism in the healthy mouse using hyperpolarized 13C magnetic resonance. Sci Rep 7:11719
Niedbalski, Peter; Parish, Christopher; Kiswandhi, Andhika et al. (2017) Influence of Dy3+ and Tb3+ doping on 13C dynamic nuclear polarization. J Chem Phys 146:014303
Moreno, Karlos X; Harrison, Crystal E; Merritt, Matthew E et al. (2017) Hyperpolarized ?-[1-13 C]gluconolactone as a probe of the pentose phosphate pathway. NMR Biomed 30:
Cheshkov, Sergey; Dimitrov, Ivan E; Jakkamsetti, Vikram et al. (2017) Oxidation of [U-13 C]glucose in the human brain at 7T under steady state conditions. Magn Reson Med 78:2065-2071
Park, Jae Mo; Khemtong, Chalermchai; Liu, Shie-Chau et al. (2017) In vivo assessment of intracellular redox state in rat liver using hyperpolarized [1-13 C]Alanine. Magn Reson Med 77:1741-1748
Jin, Eunsook S; Sherry, A Dean; Malloy, Craig R (2016) An Oral Load of [13C3]Glycerol and Blood NMR Analysis Detect Fatty Acid Esterification, Pentose Phosphate Pathway, and Glycerol Metabolism through the Tricarboxylic Acid Cycle in Human Liver. J Biol Chem 291:19031-41
Kiswandhi, Andhika; Niedbalski, Peter; Parish, Christopher et al. (2016) Impact of Ho(3+)-doping on (13)C dynamic nuclear polarization using trityl OX063 free radical. Phys Chem Chem Phys 18:21351-9
Jin, Eunsook S; Moreno, Karlos X; Wang, Jian-Xiong et al. (2016) Metabolism of hyperpolarized [1-(13)C]pyruvate through alternate pathways in rat liver. NMR Biomed 29:466-74
Ren, Jimin; Sherry, A Dean; Malloy, Craig R (2016) A simple approach to evaluate the kinetic rate constant for ATP synthesis in resting human skeletal muscle at 7 T. NMR Biomed 29:1240-8
Wang, Jian-Xiong; Merritt, Matthew E; Sherry, Dean et al. (2016) A general chemical shift decomposition method for hyperpolarized (13) C metabolite magnetic resonance imaging. Magn Reson Chem 54:665-73

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