Glutamine in the central nervous system: function and dysfunction

Albrecht, Jan

doi:10.2741/2067

Cited by 168Amino Acid Enzymes and MetabolismNeuroscience and Neuropharmacology ResearchSulfur Compounds in Biology

Glutamine in the central nervous system: function and dysfunction

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Albrecht, Jan·2007·Frontiers in Bioscience

DOI 10.2741/2067

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Abstract

Glutamine (Gln) abounds in the central nervous system (CNS), and its interstitial and cerebrospinal fluid (CSF) concentrations are at least one order of magnitude higher than of any other amino acid. Gln transport from blood to the brain is insufficient to meet the demand of the brain tissues for this amino acid. This demand is met by intracerebral Gln synthesis from glutamate (Glu), a reaction carried out by glutamine synthetase (GS), an enzyme residing in astrocytes. A major proportion of astroglia-derived Gln is shuttled to neurons where it is degraded by phosphate-activated glutaminase (PAG) giving rise to the excitatory neurotransmitter amino acid Glu, which is also a precursor of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). Glu released from neurons is taken up by astrocytes, and reconverted to Gln, closing the so called "glutamate-glutamine" cycle. A portion of Gln serves as an energy metabolite, and part of it leaves the brain to blood. Gln efflux from astrocytes, its neuronal uptake and egress to the blood via the cerebral capillary endothelial cells is mediated by different amino acid carriers showing i) considerable preference for Gln, ii) distribution between astrocytes and neurons that favors astrocyte-to-neuron fluxes of the amino acid. The Gln-specific carriers also largely contribute to Gln efflux from the brain to the vascular bed. Excessive accumulation of Gln in brain cells may be deleterious to brain function. In hyperammonemia associated with acute liver failure, excess Gln leads to cerebral edema, which largely results from its interference with mitochondrial function and partly from its osmotic action. Future analyses of the roles of Gln in both normal and abnormal cerebral metabolism and function will have to account for its newly recognized direct involvement in the regulation of gene transcription and/or translation.

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Glial cells are responsible for glutamate reuptake and facilitate the glial-astrocytic conversion of glutamate to glutamine, which limits excitotoxicity and provides necessary precursors for GABA synthesis.
“To counteract these effects, glial cells are responsible for glutamate reuptake and facilitate the glial–astrocytic conversion of glutamate to glutamine, which limits excitotoxicity and provides necessary precursors for GABA synthesis [36].”
From Pharmacotherapies Targeting GABA-Glutamate Neurotransmission for Treatment-Resistant Depression (2023) · cites this paper as [36]

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“To counteract these effects, glial cells are responsible for glutamate reuptake and facilitate the glial–astrocytic conversion of glutamate to glutamine, which limits excitotoxicity and provides necessary precursors for GABA synthesis [36].”
Background
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Authors: Albrecht, J.
Affiliations: Mossakowski Medical Research Institute, Polish Academy of Sciences (PL)
Corresponding author: Albrecht, Jan
ORCID: Albrecht, Jan
Venue: Frontiers in Bioscience
Publisher: IMR Press
Published: 2007
Volume: 12
Issue: 1
Pages: 332
ISSN: 1093-4715 (ISSN-L)
1093-9946
DOI: 10.2741/2067
OpenAlex: W2065663423
Cited by: 168
References: 118
Citations by year: 2026: 6 · 2025: 6 · 2024: 10 · 2023: 7 · 2022: 6 · 2021: 10 · 2020: 6 · 2019: 7 · 2018: 5 · 2017: 7 · 2016: 3 · 2015: 9 · 2014: 6 · 2013: 5 · 2012: 16
FWCI: 0.87
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Frontiers in bioscience (publishedVersion)
PubMed (publishedVersion)
Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Amino Acid Enzymes and Metabolism
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Sulfur Compounds in Biology
Keywords: glutamine, central nervous system, glutamine synthetase, astrocytes, glutamate, glutaminase, amino acid transporters, cerebral edema, hyperammonemia, acute liver failure, mitochondrial dysfunction, osmotic effects, gene transcription, translational regulation, brain energy metabolism
MeSH terms: Animals, Brain, Brain Chemistry, Brain Diseases, Glutamine, Humans, Mass Spectrometry, Spinal Cord, Nuclear Magnetic Resonance, Biomolecular, Hyperammonemia

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Glutamine in the central nervous system: function and dysfunction

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