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

AUTOR(ES)
FONTE

The National Academy of Sciences

RESUMO

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 ≈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 μmol/min/g (mean ± SD, n = 6), a glucose oxidation rate of 0.39 ± 0.04 μmol/min/g, and a glutamate/glutamine cycle rate of 0.32 ± 0.05 μmol/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 ≈80% of glucose oxidation.

Documentos Relacionados