We will develop and improve the spectroscopic methods needed to study tissue metabolism by (1)H Nuclear Magnetic Resonance. We will also develop computer models of metabolic pathways and design (13)C tracer experiments to test and improve these models. Finally we will perform initial experiments designed to interpret the flow of (13)C label from 1-13C glucose into lactate and glutamate in tenus of metabolic fluxes.
The specific aims are: 1. To develop 1H and 13C NMR methods to measure kinetics and steady state 13C labeling patters of lactate and amino acids in vivo. Specific areas for improvement are: i) Water Suppression (1H). ii)Sensitivity (1H, 13C). iii)Localization (1H, 13C). iv)Editing (1H). v)Quantification (1H, 13C). 2. To develop kinetic models to interpret the patterns and rates of 13C labeling of lactate and amino acids from 13C-glucose in rabbit brain. Two general areas of research are proposed: 1) To interpret the observed 13C flows into lactate and glutamate pools in terms of a computer model which only includes metabolites on the direct or linear pathway. 2) To evaluate the assumptions made in the linear model about equilibrium and contributions from other pathways.
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