Determination of the rate of the glutamate glutamine cycle in the human brain by in vivo C-13 NMR

Recent C-13 NMR studies in rat models have shown that the glutamate/glutami ne cycle is highly active in the cerebral cortex and is coupled to incremen tal glucose oxidation in an approximate to 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 glu tamate/glutamine cycle were determined in the human occipital/parietal lobe at rest. During an infusion of [1-C-13]-glucose, in vivo C-13 NMR spectra were obtained of the time courses of label incorporation into [4-C-13]-glut amate and [4-C-13]-glutamine. Using a metabolic model we have validated in the rat, we calculated a total tricarboxylic acid cycle rate of 0.77 +/- 0. 07 mu mol/min/g (mean +/- SD, n = 6), a glucose oxidation rate of 0.39 +/- 0.04 mu mol/min/g, and a glutamate/glutamine cycle rate of 0.32 +/- 0.05 pm ol/min/g (mean +/- SD, n = 6). In agreement with studies in rat cerebral co rtex, the glutamate/glutamine cycle is a major metabolic flux in the restin g human brain with a rate approximate to 80% of glucose oxidation.