Southwestern NMR Center for In Vivo Metabolism

Research Emphasis

Current Research

The facility's core research efforts focus on three projects. The first is to develop and refine the use of ¹³C nuclear magnetic resonance (NMR) isotopomer analysis for the investigation of intermediary metabolism in intact, functioning tissues and to apply these methods to current questions in metabolism. Techniques to assess human hepatic metabolism by 13C NMR of body fluids after ingestion of stable carbon isotopes and metabolite-conjugation agents have been developed.

The second project aims to develop and refine mathematical models to estimate the flux through different metabolic pathways using isotopomer analysis of ¹³C NMR and/or mass spectroscopy (MS) data. Three programs are under development: tcaSIM, a simulation of the tricarboxylic acid cycle that generates 13C isotopomer data for use in the design of experiments; tcaCALC, a model that estimates relative pathway fluxes from NMR spectra or MS data obtained at metabolic and isotopic steady state; and tcaFLUX, a kinetic analysis that allows measurement of absolute flux from systems at metabolic, but not isotopic, steady state. tcaSIM and tcaCALC are available free of charge to researchers.

The third project aims to develop new techniques and agents for monitoring intercellular cations, particularly sodium, magnesium, and calcium, in perfused tissues and in vivo. Synthetic chemistry and characterization of new agents is ongoing at the University of Texas at Dallas. Evaluation and application of the new agents for perfused organ and in vivo studies are carried out at The Advanced Imaging Research Center at The University of Texas Southwestern Medical Center

Resource Capabilities

Instruments

A range of NMR instruments (200, 300, 400, 500, and 600 MHz, including vertical- and horizontal-bore systems) is available with capabilities for both gradient-based experiments (imaging, spatially localized spectroscopy, and metabolite-specific spectroscopy) and standard spectroscopy (decoupling, magnetization transfer, multiple quantum, and two-dimensional). A bench-top gas chromatographBmass spectrometer capable of tandem MS complements the NMR data and provides an additional approach to ¹³C isotopomer analysis. Special expertise is available in isotopomer analysis of ¹³C NMR spectra, working heart perfusion preparations, synthesis of shift reagents, and in vivo MR studies. Philips 3 Tesla and 7 Tesla magnet systems will be installed in the summer of 2006.

Training Opportunities and Workshops

Annual symposium and training are offered annually in April. Please check the Web site listed above for details