A network model has been developed for analysis of tumor glucose metabolism from 13C MRS isotope exchange kinetic data. Data were obtained from DB1 melanoma cells grown on polystyrene microcarrier beads contained in a 20-mm diameter perfusion chamber in a 9.4 T Varian NMR spectrometer; the cells were perfused with 26 mM [1,6-13C2]glucose under normoxic conditions and 37°C and monitored by 13C NMR spectroscopy for 6 h. The model consists of ∼150 differential equations in the cumomer formalism describing glucose and lactate transport, glycolysis, TCA cycle, pyruvate cycling, the pentose shunt, lactate dehydrogenase, the malate-aspartate and glycerophosphate shuttles, and various anaplerotic pathways. The rate of oxygen consumption (CMRO2) was measured polarographically by monitoring differences in pO2. The model was validated by excellent agreement between model predicted and experimentally measured values of CMRO2 and glutamate pool size. Assuming a P/O ratio of 2.5 for NADH and 1.5 for FADH2, ATP production was estimated as 46% glycolytic and 54% mitochondrial based on average values of CMRO2 and glycolytic flux (two experiments).
Melanoma Aerobic glycolysis
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This research was supported by NIH grants 2U24-CA083105-10 (JDG), P41RR08079 (AAS), and R01NS3867 (AAS). The authors thank Dr. Edwin M. Chance for inspiration and helpful discussion and David S. Nelson for assistance in preparing this manuscript.
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