Determination of the rate of the glutamate/glutamine cycle in the human brain by in vivo 13C NMR |
| |
Authors: | Jun Shen Kitt F. Petersen Kevin L. Behar Peter Brown Terrence W. Nixon Graeme F. Mason Ognen A. C. Petroff Gerald I. Shulman Robert G. Shulman Douglas L. Rothman |
| |
Affiliation: | Division of Medical Physics, Nathan S. Kline Institute for Psychiatric Research, Orangeburg, NY 10962, USA. |
| |
Abstract: | 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. |
| |
Keywords: | |
|
|