GABA, glutamate and glutamine: the pathway in the body

This page shows the biochemical pathway behind the laboratory value GABA, glutamate, glutamine: which stations follow one another, which enzymes carry out each step and which cofactors they use. Every statement has a source. The page describes general textbook knowledge and says nothing about any individual person.

In brief

Glutamate and GABA are messengers of the nervous system: glutamate excites, GABA inhibits. Nerve cells make GABA from glutamate, and astrocytes resupply both via glutamine.

The pathway step by step

1. Glutamine → Glutamate Glutaminase The enzyme glutaminase removes an amino group from glutamine, forming glutamate, the brain's main excitatory messenger. Source 1, 4
2. Glutamate → GABA GAD65, GAD67 · Vitamin B6 (PLP) In certain nerve cells, glutamate decarboxylase (GAD65, GAD67) removes a carboxyl group from glutamate, forming GABA, the main inhibitory messenger. The enzyme needs pyridoxal phosphate, the active form of vitamin B6. Source 3, 2
3. GABA → Synaptic cleft · VGAT, VGLUT (vesicle) Vesicular transporters load GABA and glutamate into storage vesicles. On a signal, the cells release the contents into the gap between two nerve cells, where they bind to receptors. Source 1, 2
4. In the astrocyte → Glutamine (astrocyte) Glutamine synthetase · ATP, Ammonia Glutamine synthetase adds an amino group from ammonia to glutamate, using up ATP. The astrocyte passes the glutamine back to the nerve cell, closing the cycle. Source 1, 4
5. In the astrocyte → Succinic semialdehyde GABA transaminase · Vitamin B6 (PLP), α-Ketoglutarate GABA transaminase transfers the amino group of GABA to α-ketoglutarate. This yields succinic semialdehyde and glutamate. This enzyme also works with pyridoxal phosphate. Source 4, 1
6. Succinic semialdehyde → Succinate SSADH · NAD⁺ Succinic semialdehyde dehydrogenase turns it into succinate, an intermediate of the citric acid cycle. Via this shunt, GABA flows back into energy metabolism. Source 4, 2

Cofactors in this pathway

• Vitamin B6 (PLP) — Cofactor of glutamate decarboxylase, which forms GABA, and of GABA transaminase Source 3, 4In the ORY catalogue as a laboratory value: Vitamin B6
• Magnesium — Metal ion and part of Mg-ATP at the active site of glutamine synthetase Source 7In the ORY catalogue as a laboratory value: Magnesium
• α-Ketoglutarate — Accepts the amino group from GABA at GABA transaminase Source 4, 1In the ORY catalogue as a laboratory value: Alpha-Ketoglutarat (2-Oxoglutarat)
• NAD⁺ — Accepts hydrogen when SSADH converts succinic semialdehyde to succinate Source 4In the ORY catalogue as a laboratory value: NAD⁺ (Nicotinamidadenindinukleotid)
• Sodium — The transporters EAAT1 and EAAT2 carry glutamate into the astrocyte together with sodium Source 5In the ORY catalogue as a laboratory value: Natrium (intrazellulär)
• Potassium — Moved out of the cell in exchange during glutamate transport via EAAT Source 5In the ORY catalogue as a laboratory value: Kalium (intrazellulär)

What acts on this pathway

• Vigabatrin — Vigabatrin binds irreversibly to GABA transaminase. The prescribing information states that GABA is therefore broken down more slowly and is present in higher amounts in the nervous system. Source 6

Sources

1. Bak LK, Schousboe A, Waagepetersen HS. The glutamate/GABA-glutamine cycle: aspects of transport, neurotransmitter homeostasis and ammonia transfer. J Neurochem 2006 · PubMed 16787421
2. Andersen JV, Schousboe A et al. Milestone Review: Metabolic dynamics of glutamate and GABA mediated neurotransmission - The essential roles of astrocytes. J Neurochem 2023 · PubMed 36919769
3. Martin DL, Rimvall K. Regulation of gamma-aminobutyric acid synthesis in the brain. J Neurochem 1993 · PubMed 8419527
4. Waagepetersen HS, Sonnewald U, Schousboe A. Compartmentation of glutamine, glutamate, and GABA metabolism in neurons and astrocytes: functional implications. Neuroscientist 2003 · PubMed 14580123
5. Danbolt NC. Glutamate uptake. Prog Neurobiol 2001 · PubMed 11369436
6. US prescribing information Vigabatrin (DailyMed), section 12.1 Mechanism of Action · Prescribing information
7. Eisenberg D, Gill HS, Pfluegl GM et al. Structure-function relationships of glutamine synthetases. Biochim Biophys Acta 2000 · PubMed 10708854

Related pathways

• Alanine — glutamate
• Citric acid cycle — succinate
• Branched-chain amino acids — Vitamin B6, Alpha-Ketoglutarat (2-Oxoglutarat)
• Carnitine — Vitamin B6, Alpha-Ketoglutarat (2-Oxoglutarat)
• Glycine and serine — Vitamin B6, Magnesium

As of 2026-09-16. Draft written by Claude to schema v2; sources checked in PubMed; expert review pending
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