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Departments of 1 Radiology, 2 Medicine, and 3 Biochemistry, Center for Magnetic Resonance Research and General Clinical Research Center, University of Minnesota, Minneapolis, Minnesota 55455
After administration of enriched
[1-13C]glucose, the rate of 13C label
incorporation into glutamate C4, C3, and C2, glutamine C4, C3, and C2,
and aspartate C2 and C3 was simultaneously measured in six normal
subjects by 13C NMR at 4 Tesla in 45-ml volumes
encompassing the visual cortex. The resulting eight time courses were
simultaneously fitted to a mathematical model. The rate of (neuronal)
tricarboxylic acid cycle flux (VPDH), 0.57 ± 0.06 µmol · g
1 · min1,
was comparable to the exchange rate between (mitochondrial) 2-oxoglutarate and (cytosolic) glutamate (Vx,
0.57 ± 0.19 µmol · g1 · min1), which
may reflect to a large extent malate-aspartate shuttle activity. At
rest, oxidative glucose consumption [CMRGlc(ox)] was
0.41 ± 0.03 µmol · g1 · min1, and
(glial) pyruvate carboxylation (VPC) was
0.09 ± 0.02 µmol · g1 · min1. The
flux through glutamine synthetase (Vsyn) was
0.26 ± 0.06 µmol · g1 · min1. A
fraction of Vsyn was attributed to be from
(neuronal) glutamate, and the corresponding rate of apparent
glutamatergic neurotransmission (VNT) was
0.17 ± 0.05 µmol · g1 · min1. The
ratio [VNT/CMRGlc(ox)] was
0.41 ± 0.14 and thus clearly different from a 1:1 stoichiometry,
consistent with a significant fraction (~90%) of ATP generated in
astrocytes being oxidative. The study underlines the importance of
assumptions made in modeling 13C labeling data in brain.
nuclear magnetic resonance; glutamate; neurotransmission; in vivo spectroscopy
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