CEREBRAL METABOLIC COMPARTMENTATION AS REVEALED BY NUCLEAR-MAGNETIC-RESONANCE ANALYSIS OF D-[1-13C]GLUCOSE METABOLISM

Nuclear magnetic resonance (NMR) was used to study the metabolic pathw ays involved in the conversion of glucose to glutamate, gamma-aminobut yrate (GABA), glutamine, and aspartate. D-[1-C-13]Glucose was administ ered to rats intraperitoneally, and 6, 1 5, 30, or 45 min later the ra ts were killed and extracts from the forebrain were prepared for C-13- NMR analysis and amino acid analysis. The absolute amount of C-13 pres ent 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 f or C-3 of lactate. The natural abundance C-13 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 glutamat e and GABA indicates that these amino acids were synthesized primarily within compartments in which glucose was metabolized to pyruvate, fol lowed by decarboxylation to acetyl-CoA for entry into the tricarboxyli c acid cycle. In contrast, the labeling pattern for glutamine and aspa rtate indicates that appreciable amounts of these amino acids were syn thesized within a compartment in which glucose was metabolized to pyru vate, followed by carboxylation to oxaloacetate. These results are con sistent with the concept that pyruvate carboxylase and glutamine synth etase 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 glu tamate, 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 replenish ing the neurotransmitter pool of GABA. However, a similar role for ast rocytes in replenishing the transmitter pool of glutamate was not subs tantiated, possibly due to difficulties in quantitating satellite peak s arising from C-13-C-13 coupling.