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Measurements of the anaplerotic rate in the human cerebral cortex using 13 C magnetic resonance spectroscopy and [1‐ 13 C] and [2‐ 13 C] glucose
Author(s) -
Mason Graeme F.,
Petersen Kitt Falk,
De Graaf Robin A.,
Shulman Gerald I.,
Rothman Douglas L.
Publication year - 2007
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.04200.x
Subject(s) - glutamine , glutamate receptor , pyruvate carboxylase , biochemistry , biology , glutamic acid , citric acid cycle , glutamate dehydrogenase , metabolism , enzyme , amino acid , receptor
Recent studies in rodent and human cerebral cortex have shown that glutamate‐glutamine neurotransmitter cycling is rapid and the major pathway of neuronal glutamate repletion. The rate of the cycle remains controversial in humans, because glutamine may come either from cycling or from anaplerosis via glial pyruvate carboxylase. Most studies have determined cycling from isotopic labeling of glutamine and glutamate using a [1‐ 13 C]glucose tracer, which provides label through neuronal and glial pyruvate dehydrogenase or via glial pyruvate carboxylase. To measure the anaplerotic contribution, we measured 13 C incorporation into glutamate and glutamine in the occipital‐parietal region of awake humans while infusing [2‐ 13 C]glucose, which labels the C2 and C3 positions of glutamine and glutamate exclusively via pyruvate carboxylase. Relative to [1‐ 13 C]glucose, [2‐ 13 C]glucose provided little label to C2 and C3 glutamine and glutamate. Metabolic modeling of the labeling data indicated that pyruvate carboxylase accounts for 6 ± 4% of the rate of glutamine synthesis, or 0.02 μmol/g/min. Comparison with estimates of human brain glutamine efflux suggests that the majority of the pyruvate carboxylase flux is used for replacing glutamate lost due to glial oxidation and therefore can be considered to support neurotransmitter trafficking. These results are consistent with observations made with arterial–venous differences and radiotracer methods.