TY - JOUR
T1 - Modeling of brain metabolism and pyruvate compartmentation using 13 C NMR in vivo
T2 - Caution required
AU - Jeffrey, F. Mark
AU - Marin-Valencia, Isaac
AU - Good, Levi B.
AU - Shestov, Alexander A.
AU - Henry, Pierre Gilles
AU - Pascual, Juan M.
AU - Malloy, Craig R.
PY - 2013/8
Y1 - 2013/8
N2 - Two variants of a widely used two-compartment model were prepared for fitting the time course of [1,6-13 C 2 ]glucose metabolism in rat brain. Features common to most models were included, but in one model the enrichment of the substrates entering the glia and neuronal citric acid cycles was allowed to differ. Furthermore, the models included the capacity to analyze multiplets arising from 13 C spin-spin coupling, known to improve parameter estimates in heart. Data analyzed were from a literature report providing time courses of [1,6-13 C 2 ]glucose metabolism. Four analyses were used, two comparing the effect of different pyruvate enrichment in glia and neurons, and two for determining the effect of multiplets present in the data. When fit independently, the enrichment in glial pyruvate was less than in neurons. In the absence of multiplets, fit quality and parameter values were typical of those in the literature, whereas the multiplet curves were not modeled well. This prompted the use of robust statistical analysis (the Kolmogorov-Smirnov test of goodness of fit) to determine whether individual curves were modeled appropriately. At least 50% of the curves in each experiment were considered poorly fit. It was concluded that the model does not include all metabolic features required to analyze the data.
AB - Two variants of a widely used two-compartment model were prepared for fitting the time course of [1,6-13 C 2 ]glucose metabolism in rat brain. Features common to most models were included, but in one model the enrichment of the substrates entering the glia and neuronal citric acid cycles was allowed to differ. Furthermore, the models included the capacity to analyze multiplets arising from 13 C spin-spin coupling, known to improve parameter estimates in heart. Data analyzed were from a literature report providing time courses of [1,6-13 C 2 ]glucose metabolism. Four analyses were used, two comparing the effect of different pyruvate enrichment in glia and neurons, and two for determining the effect of multiplets present in the data. When fit independently, the enrichment in glial pyruvate was less than in neurons. In the absence of multiplets, fit quality and parameter values were typical of those in the literature, whereas the multiplet curves were not modeled well. This prompted the use of robust statistical analysis (the Kolmogorov-Smirnov test of goodness of fit) to determine whether individual curves were modeled appropriately. At least 50% of the curves in each experiment were considered poorly fit. It was concluded that the model does not include all metabolic features required to analyze the data.
KW - [1,6-13C2]glucose
KW - cerebral energy metabolism
KW - in vivo 13C NMR spectroscopy
KW - mathematical modeling
KW - rat
KW - tricarboxylic acid cycle
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U2 - 10.1038/jcbfm.2013.67
DO - 10.1038/jcbfm.2013.67
M3 - Article
C2 - 23652627
AN - SCOPUS:84881142709
SN - 0271-678X
VL - 33
SP - 1160
EP - 1167
JO - Journal of Cerebral Blood Flow and Metabolism
JF - Journal of Cerebral Blood Flow and Metabolism
IS - 8
ER -