Determination of the rate of the glutamate/glutamine cycle in the human brain by in vivo 13 C NMR
Open accessAbstract
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.
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The same stoichiometric coupling applies to rat and human cerebral cortex in vivo.
“Remarkably, these studies have shown that the same stoichiometric coupling applies to rat [32] and human [33] cerebral cortex in vivo.”
From Scaling of Brain Metabolism with a Fixed Energy Budget per Neuron: Implications for Neuronal Activity, Plasticity and Evolution (2011) · cites this paper as [33]
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- Authors
- Shen, J., Petersen, K. F., Behar, K. L., Brown, P., Nixon, T. W., Mason, G. F., Petroff, O. A. C., Shulman, G. I., Shulman, R. G., & Rothman, D. L.
- Affiliations
- Nathan Kline Institute for Psychiatric Research (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1999-07-06
- Volume
- 96
- Issue
- 14
- Pages
- 8235-8240
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC22218
- OpenAlex
- W2052750469
- Cited by
- 462
- References
- 55
- Citations by year
- 2026: 10 · 2025: 14 · 2024: 7 · 2023: 10 · 2022: 15 · 2021: 15 · 2020: 14 · 2019: 10 · 2018: 12 · 2017: 20 · 2016: 12 · 2015: 7 · 2014: 25 · 2013: 29 · 2012: 24
- FWCI
- 21.43
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Yale University
- National Institutes of Health (DK-45735)
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK049230, R01DK040936, R01DK027121, P30DK045735)
- National Institute of Neurological Disorders and Stroke (R29NS032126, R01-NS032515, P01-NS 06208, R01NS037527, R01NS034813)
- National Center for Research Resources (M01RR000125)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Advanced MRI Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- glutamate-glutamine cycle, cerebral cortex, TCA cycle, glucose oxidation, glutamine synthesis, metabolic flux, metabolic modeling
- MeSH terms
- Adult, Animals, Carbon Isotopes, Cerebral Cortex, Citric Acid Cycle, Female, Glucose, Glutamine, Humans, Kinetics, Male, Models, Chemical, Magnetic Resonance Spectroscopy, Oxidation-Reduction, Parietal Lobe, Reference Values, Temporal Lobe, Time Factors, Glutamic Acid, Rats
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