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The endogenous substance pyruvate is of major importance to maintain energy homeostasis in the cells and provides a window to several important metabolic processes essential to cell survival. Cell viability is therefore reflected in the metabolism of pyruvate. NMR spectroscopy has until now been the only noninvasive method to gain insight into the fate of pyruvate in the body, but the low NMR sensitivity even at high field strength has only allowed information about steady-state conditions. The medically relevant information about the distribution, localization, and metabolic rate of the substance during the first minute after the injection has not been obtainable. Use of a hyperpolarization technique has enabled 10 -15% polarization of 13 C1 in up to a 0.3 M pyruvate solution. i.v. injection of the solution into rats and pigs allows imaging of the distribution of pyruvate and mapping of its major metabolites lactate and alanine within a time frame of Ϸ10 s. Real-time molecular imaging with MRI has become a reality.13 C ͉ dynamic nuclear polarization ͉ hyperpolarized ͉ MRI ͉ spectroscopy T he technique for increase in signal-to-noise ratio of Ͼ10,000 times in liquid-state NMR and the use of this technique for molecular imaging with endogenous substances generated through the process of dynamic nuclear polarization (DNP) has been reported (1, 2). In both these studies, 13 C-enriched urea was used as an example of an endogenous substance that could be polarized to a high degree (37% for 13 C and 8% for 15 N) and used for high-resolution imaging of the cardiovascular system in rats.It was suggested that the signal enhancement could be used not only for visualizing the cardiovascular system but also for improved perfusion measurements and that it may allow realtime metabolic mapping of other endogenous substances such as alanine, glutamine, and acetate. Such studies should be possible if the relaxation time of the 13 C-labeled site in the hyperpolarized molecule is long enough and the metabolic products retain sufficient fraction of the nonequilibrium polarization. The possibilities for doing perfusion studies using 13 C labeled hyperpolarized substances have recently been reviewed by Månsson et al. (3), but the application of visualizing metabolic processes by using hyperpolarized substances have not yet been described.To reveal information about the metabolic status of the tissue, magnetic resonance (MR) spectroscopy has been used, employing nuclei like 1 H, 13 C, 31 P, and 19 F (4, 5). The main application areas have been brain, muscle, and prostate tissue. Information on fluxes through metabolic pathways is less straightforward to obtain though. Traditionally, 13 C NMR spectroscopy in combination with 13 C-labeled (enriched) substrates has been used to visualize the label applied, its metabolic intermediates, and͞or its end products during steady-state conditions. In certain cases the metabolic rates can be indirectly estimated by using mathematical modeling (6), for example, in determining the flux through the...
The endogenous substance pyruvate is of major importance to maintain energy homeostasis in the cells and provides a window to several important metabolic processes essential to cell survival. Cell viability is therefore reflected in the metabolism of pyruvate. NMR spectroscopy has until now been the only noninvasive method to gain insight into the fate of pyruvate in the body, but the low NMR sensitivity even at high field strength has only allowed information about steady-state conditions. The medically relevant information about the distribution, localization, and metabolic rate of the substance during the first minute after the injection has not been obtainable. Use of a hyperpolarization technique has enabled 10 -15% polarization of 13 C1 in up to a 0.3 M pyruvate solution. i.v. injection of the solution into rats and pigs allows imaging of the distribution of pyruvate and mapping of its major metabolites lactate and alanine within a time frame of Ϸ10 s. Real-time molecular imaging with MRI has become a reality.13 C ͉ dynamic nuclear polarization ͉ hyperpolarized ͉ MRI ͉ spectroscopy T he technique for increase in signal-to-noise ratio of Ͼ10,000 times in liquid-state NMR and the use of this technique for molecular imaging with endogenous substances generated through the process of dynamic nuclear polarization (DNP) has been reported (1, 2). In both these studies, 13 C-enriched urea was used as an example of an endogenous substance that could be polarized to a high degree (37% for 13 C and 8% for 15 N) and used for high-resolution imaging of the cardiovascular system in rats.It was suggested that the signal enhancement could be used not only for visualizing the cardiovascular system but also for improved perfusion measurements and that it may allow realtime metabolic mapping of other endogenous substances such as alanine, glutamine, and acetate. Such studies should be possible if the relaxation time of the 13 C-labeled site in the hyperpolarized molecule is long enough and the metabolic products retain sufficient fraction of the nonequilibrium polarization. The possibilities for doing perfusion studies using 13 C labeled hyperpolarized substances have recently been reviewed by Månsson et al. (3), but the application of visualizing metabolic processes by using hyperpolarized substances have not yet been described.To reveal information about the metabolic status of the tissue, magnetic resonance (MR) spectroscopy has been used, employing nuclei like 1 H, 13 C, 31 P, and 19 F (4, 5). The main application areas have been brain, muscle, and prostate tissue. Information on fluxes through metabolic pathways is less straightforward to obtain though. Traditionally, 13 C NMR spectroscopy in combination with 13 C-labeled (enriched) substrates has been used to visualize the label applied, its metabolic intermediates, and͞or its end products during steady-state conditions. In certain cases the metabolic rates can be indirectly estimated by using mathematical modeling (6), for example, in determining the flux through the...
The sections in this article are: Overall Renal Handling Mono‐, Di‐, and Tricarboxylates Sulfate and Thiosulfate Tubular Handling as Studied by Micropuncture and Microperfusion Monocarboxylates Di‐ftricarboxylates Sulfate/Thiosulfate Transport in Isolated Membrane Vesicles Monocarboxylates Di‐ltricarboxylates Sulfate/Thiosulfate Characterization of Proteins Involved in Transmembrane Transport Reconstitution of Mono‐, Di‐, and Tricarboxylate Transport in Artificial Liposomes Partial Purification of a Dicarboxylic Acid‐Binding Protein Identification of a Protein Involved in Basolateral Sulfate Transport Cellular Models Monocarboxylates Di‐/tricarboxylates Sulfate/Thiosulfate
The sections in this article are: Methodological Considerations Coupling of Metabolism to Transport Oxidative vs. Glycolytic Metabolism in the Mammalian Kidney Stoichiometry of Transepithelial Na + Transport to QO 2 Transport as the Pacemaker of Respiration Control of Transport by Metabolism Metabolic Substrate Utilization by the Kidney Metabolic Heterogeneity of the Kidney Metabolism of Glucose Lactate Metabolism Pyruvate Metabolism Renal Lipid Metabolism Amino Acid Metabolism Citrate Metabolism Ketone Metabolism Synthetic Functions of the Kidney Gluconeogenesis Alanine Serine Renal Phospholipid Metabolism Phospholipid Composition of Kidney Metabolism of Specific Renal Phospholipids Metabolism of Membrane Proteins in Kidney Phosphorylation of Membrane Proteins ADP ‐Ribosylation
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