Determination of the rate of the glutamate/glutamine cycle in the human brain by in vivo 13C NMR.
Recent 13C NMR studies in rat models have shown that the glutamate/glutamine cycle is highly active in the cerebral cortex and is coupled to incremental glucose oxidation in an approximately 1:1 stoichiometry. To determine whether a high level of glutamatergic activity is present in human cortex, the rates of the tricarboxylic acid cycle, glutamine synthesis, and the glutamate/glutamine cycle were determined in the human occipital/parietal lobe at rest. During an infusion of [1-13C]-glucose, in vivo 13C NMR spectra were obtained of the time courses of label incorporation into [4-13C]-glutamate and [4-13C]-glutamine. Using a metabolic model we have validated in the rat, we calculated a total tricarboxylic acid cycle rate of 0.77 +/- 0.07 micromol/min/g (mean +/- SD, n = 6), a glucose oxidation rate of 0.39 +/- 0.04 micromol/min/g, and a glutamate/glutamine cycle rate of 0.32 +/- 0.05 micromol/min/g (mean +/- SD, n = 6). In agreement with studies in rat cerebral cortex, the glutamate/glutamine cycle is a major metabolic flux in the resting human brain with a rate approximately 80% of glucose oxidation.
Division of Medical Physics, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA.
J
J
Shen
K F
KF
Petersen
K L
KL
Behar
P
P
Brown
T W
TW
Nixon
G F
GF
Mason
O A
OA
Petroff
G I
GI
Shulman
R G
RG
Shulman
D L
DL
Rothman
D000328:Adult; D000818:Animals; D002247:Carbon Isotopes; D002540:Cerebral Cortex / Q000378:metabolism*; D002952:Citric Acid Cycle; D005260:Female; D005947:Glucose / Q000378:metabolism*; D018698:Glutamic Acid / Q000378:metabolism*; D005973:Glutamine / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008956:Models, Chemical; D010084:Oxidation-Reduction; D010296:Parietal Lobe / Q000378:metabolism; D051381:Rats; D012016:Reference Values; D013702:Temporal Lobe / Q000378:metabolism; D013997:Time Factors
D002247:Carbon Isotopes; D005973:Glutamine; D018698:Glutamic Acid; D005947:Glucose