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Cerebral Metabolic Compartmentation as Revealed by Nuclear Magnetic Resonance Analysis of D‐[1‐ 13 C]Glucose Metabolism
Author(s) -
Shank Richard P.,
Leo Gregory C.,
Zielke H. Ronald
Publication year - 1993
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.1471-4159.1993.tb03570.x
Subject(s) - glutamine , biochemistry , taurine , citric acid cycle , pyruvate carboxylase , metabolism , glutamate receptor , amino acid , gluconeogenesis , citrate synthase , tricarboxylic acid , biology , decarboxylation , alanine , chemistry , enzyme , receptor , catalysis
Nuclear magnetic resonance (NMR) was used to study the metabolic pathways involved in the conversion of glucose to glutamate, γ‐aminobutyrate (GABA), glutamine, and aspartate. d ‐[1 ‐13 C]Glucose was administered to rats intraperitoneally, and 6, 15, 30, or 45 min later the rats were killed and extracts from the forebrain were prepared for 13 C‐NMR analysis and amino acid analysis. The absolute amount of 13 C present within each carbon‐atom pool was determined for C‐2, C‐3, and C‐4 of glutamate, glutamine, and GABA, for C‐2 and C‐3 of aspartate, and for C‐3 of lactate. The natural abundance 13 C present in extracts from control rats was also determined for each of these compounds and for N ‐acetylaspartate and taurine. The pattern of labeling within glutamate and GABA indicates that these amino acids were synthesized primarily within compartments in which glucose was metabolized to pyruvate, followed by decarboxylation to acetyl‐CoA for entry into the tricarboxylic acid cycle. In contrast, the labeling pattern for glutamine and aspartate indicates that appreciable amounts of these amino acids were synthesized within a compartment in which glucose was metabolized to pyruvate, followed by carboxylation to oxaloacetate. These results are consistent with the concept that pyruvate carboxylase and glutamine synthetase are glia‐specific enzymes, and that this partially accounts for the unusual metabolic compartmentation in CNS tissues. The results of our study also support the concept that there are several pools of glutamate, with different metabolic turnover rates. Our results also are consistent with the concept that glutamine and/or a tricarboxylic acid cycle intermediate is supplied by astrocytes to neurons for replenishing the neurotransmitter pool of GABA. However, a similar role for astrocytes in replenishing the transmitter pool of glutamate was not substantiated, possibly due to difficulties in quantitating satellite peaks arising from 13 C‐ 13 C coupling.