The glutamate/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer

Bak, Lasse K.; Schousboe, Arne; Waagepetersen, Helle S.

doi:10.1111/j.1471-4159.2006.03913.x

Cited by 1,114Amino Acid Enzymes and MetabolismNeuroscience and Neuropharmacology ResearchSulfur Compounds in Biology

The glutamate/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer

Bak, Lasse K., Schousboe, Arne, Waagepetersen, Helle S.·2006·Journal of Neurochemistry

DOI 10.1111/j.1471-4159.2006.03913.x

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Abstract

Neurons are metabolically handicapped in the sense that they are not able to perform de novo synthesis of neurotransmitter glutamate and gamma-aminobutyric acid (GABA) from glucose. A metabolite shuttle known as the glutamate/GABA-glutamine cycle describes the release of neurotransmitter glutamate or GABA from neurons and subsequent uptake into astrocytes. In return, astrocytes release glutamine to be taken up into neurons for use as neurotransmitter precursor. In this review, the basic properties of the glutamate/GABA-glutamine cycle will be discussed, including aspects of transport and metabolism. Discussions of stoichiometry, the relative role of glutamate vs. GABA and pathological conditions affecting the glutamate/GABA-glutamine cycling are presented. Furthermore, a section is devoted to the accompanying ammonia homeostasis of the glutamate/GABA-glutamine cycle, examining the possible means of intercellular transfer of ammonia produced in neurons (when glutamine is deamidated to glutamate) and utilized in astrocytes (for amidation of glutamate) when the glutamate/GABA-glutamine cycle is operating. A main objective of this review is to endorse the view that the glutamate/GABA-glutamine cycle must be seen as a bi-directional transfer of not only carbon units but also nitrogen units.

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Glutamate can also be synthesized from the tricarboxylic acid cycle.
“glutamate can also be synthesized from the tricarboxylic acid cycle 62”
From Glutamate in Schizophrenia: A Focused Review and Meta-Analysis of 1H-MRS Studies (2013) · cites this paper as [62]
Glutamine is the major precursor for neuronal glutamate (and GABA).
“while glutamine represents the major precursor for neuronal glutamate (and GABA)”
From Glutamate in Schizophrenia: A Focused Review and Meta-Analysis of 1H-MRS Studies (2013) · cites this paper as [62]

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Authors: Bak, L. K., Schousboe, A., & Waagepetersen, H. S.
Corresponding author: Bak, Lasse K.
ORCID: Bak, Lasse K.
Schousboe, Arne
Waagepetersen, Helle S.
Venue: Journal of Neurochemistry
Publisher: Wiley
Published: 2006-06-19
Volume: 98
Issue: 3
Pages: 641-653
ISSN: 0022-3042 (ISSN-L)
1471-4159
DOI: 10.1111/j.1471-4159.2006.03913.x
OpenAlex: W1992521533
Cited by: 1,114
References: 125
Citations by year: 2026: 51 · 2025: 84 · 2024: 82 · 2023: 97 · 2022: 100 · 2021: 83 · 2020: 83 · 2019: 58 · 2018: 48 · 2017: 58 · 2016: 70 · 2015: 50 · 2014: 48 · 2013: 44 · 2012: 30
FWCI: 2.24
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor)
Locations: Journal of Neurochemistry (publishedVersion)
PubMed (publishedVersion)
Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders: H. Lundbeck A/S
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: glutamate uptake, GABA uptake, glutamine transport, astrocytes, neurotransmitter homeostasis, glutamine deamidation, nitrogen transfer, neuronal metabolism
MeSH terms: Ammonia, Animals, Biological Transport, gamma-Aminobutyric Acid, Glutamine, Homeostasis, Humans, Glutamic Acid

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The glutamate/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer

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