This application is for the purchase of a narrow bore 600 MHz NMR spectrometer which will be placed in an established NMR spectroscopy center. A common interest of this group of investigators is the application of (13)C and (1)H NMR isotopomer analysis for metabolic studies. Over the last 10 years we have developed the tools for unraveling the metabolic information provided by (13)C-(13)C and (13)C-(1)H coupling in tissues metabolizing (13)C enriched compounds. Although these methods were refined largely for interpretation of spectra from the isolated heart, it has become clear over the last year that isotopomer analysis is applicable to quantitation of complex pathways in other tissues and for metabolic studies in humans. The basic reason for this request is to improve sensitivity and chemical shift dispersion to allow more reliable quantitative analysis of metabolic pathways. This advance will allow the use of smaller samples including the isolated mouse heart or a few mls of human blood, better time resolution in our kinetic studies of intact tissues, and additional (13)C fractional enrichment data provided by a single 2D heteronuclear multiple bond correlation spectrum, all of which will dramatically improve our ability to exploit the power of isotopomer analysis to interrogate intermediary metabolism. Our view is that for the next decade, at least, the single most fruitful method for the analysis of intermediary metabolism will be (13)C and (1)H NMR spectroscopy. Although in vivo (1)H and (13)C NMR spectroscopy is the most exciting application of isotopomer analysis, it is unlikely that appropriate whole-body MRI/MRS systems at the necessary field will be widely available any time soon for clinical research. On the other hand, analytical NMR spectrometers suitable for isotopomer studies of human blood or urine are already in place in virtually every medical school in this country. We will apply these powerful methods in cell culture, small animal models and in human volunteers, with the ultimate goal of using isotopomer analysis for evaluation of intermediary metabolism in patients.
| Carvalho, Rui A; Jones, John G; McGuirk, Chris et al. (2002) Hepatic gluconeogenesis and Krebs cycle fluxes in a CCl4 model of acute liver failure. NMR Biomed 15:45-51 |
| Jones, J G; Carvalho, R A; Sherry, A D et al. (2000) Quantitation of gluconeogenesis by (2)H nuclear magnetic resonance analysis of plasma glucose following ingestion of (2)H(2)O. Anal Biochem 277:121-6 |
| Carvalho, R A; Babcock, E E; Jeffrey, F M et al. (1999) Multiple bond 13C-13C spin-spin coupling provides complementary information in a 13C NMR isotopomer analysis of glutamate. Magn Reson Med 42:197-200 |
| Carvalho, R A; Jeffrey, F M; Sherry, A D et al. (1998) C isotopomer analysis of glutamate by heteronuclear multiple quantum coherence-total correlation spectroscopy (HMQC-TOCSY). FEBS Lett 440:382-6 |
