What Is The Role Of Glutamate And GABA In The Body?

This guide covers the role of Glutamate and GABA in the body.

Glutamate and GABA (gamma-aminobutyric acid) are important neurotransmitters in the body. Neurotransmitters are chemical messengers that pass on electric impulses from one cell to another.

Most neurotransmitters of the body are amino acids. Neurotransmitters can either be excitatory or inhibitory based on the type of signals they transmit.

A balanced firing of excitatory and inhibitory impulses is required for the brain to function appropriately. Glutamate controls the excitatory impulses while GABA regulates the inhibitory impulses.

GABA is produced in the brain via the action of an enzyme, glutamic acid decarboxylase (GAD) that facilitates the irreversible decarboxylation of glutamate.

The synthesis of glutamate in the brain occurs from the transamination of alpha-ketoglutarate and also the deamination of glutamine.

Role of Glutamate In the Gut-Brain Axis

Research has demonstrated a connection between the digestive tract and the brain, referred to as the gut-brain axis. This axis helps to coordinate and maintain gut functions, while simultaneously modulating brain functions. Glutamate particularly plays an essential role in this axis.

Glutamate is present in the gut as a product of the digestion of dietary proteins, food additives such as Monosodium Glu as well as seafood. However, dietary glutamate does not normally get absorbed into the brain. The functions of glutamate in the gut are as follows:

• Glutamate from diet partakes in the production of essential amino acids such as Proline, Arginine, Citrulline, and Glutathione.
• Glutamate is also needed for transmitting taste signals.
• In the esophagus and stomach and intestine, Glutamate affects motility and the secretion of digestive juices.

Glutamate enhances gastric motility and could be used in conditions with gut dysmotility. However, glutamate has been implicated in worsening symptoms of irritable bowel disease and inflammatory bowel syndrome.

In the brain, glutamate helps in crucial functions such as learning, memory, behavior and cognition. Ironically, it is toxic to nerve cells when present in the extracellular fluid, a phenomenon known as ‘excitotoxicity’. As such, it is constantly being taken away from the ECF as soon as it is released by cells and it plays a role in the pathogenesis of neurodegenerative diseases like motor neuron disease, Huntington’s disease, and Parkinson’s disease.

Functions of GABA in the body

GABA, the main inhibitory neurotransmitter of the body is involved in functions of the brain such as behavior, mood, sleep, and cognition. GABA carries out its effects via receptors known as GABA_A and GABA_B receptors. GABA_A  receptors exert a fast inhibitory effect and function by allowing chloride ions to move into the nerve cells. On the other hand, GABA_B receptors have a slow inhibitory effect and act by reducing the entry of calcium ions into the neurons.

Disordered functioning of the GABAergic system has been found in some diseases:

1. Epilepsy: Low levels of GABA in the body lead to an imbalance in the excitatory-inhibitory system of the brain. Brain cells have reduced inhibitory signals making them persist in an excitatory state. As a result of this hyperactivity, seizures could occur.
2. Sleep disorders: GABA plays a key role in regulating the sleep cycle, hence altered GABA neurotransmission could manifest as insomnia.
3. Generalized anxiety: Reduced GABA levels lead to a feeling of anxiousness because of the loss of inhibition on the nerve cells.
4. Schizophrenia: Though the exact pathway by which schizophrenia occurs is not fully understood, one of the hypotheses maintains that GABAergic system dysfunction is a likely cause. This hypothesis is supported by the effectiveness of drugs that promote GABA receptor functions in this condition.
5. Depression: Reduced levels of GABA neurotransmitters have been reported in patients with depression.
6. Alcohol use disorder: Alcohol works on the brain by acting on GABA receptors and enhancing their function. However, prolonged intake of alcohol leads to tolerance and alters the function of GABA receptors causing dependence.

GABA is also found in other organs of the body such as the pancreas. Its role in pancreatic function has recently gained a lot of interest. Preliminary studies conducted on animal models have shown that GABA helps pancreatic cells to regenerate. It also helps in controlling the release of insulin from the beta cells of the pancreas as well as the release of glucagon from the alpha cells. These two hormones, insulin and glucagon are essential for glucose metabolism in the body. Furthermore, GABA has been shown to prevent inflammatory and autoimmune responses that destroy the cells of the pancreas, which are both central events leading to diabetes. When taken orally, GABA decreases glucose levels by improving insulin secretion in patients with diabetes. Its safety for use in humans has also been proven. Other beneficial effects of GABA in diabetes include: reducing insulin resistance, improving glucose tolerance, and preserving the insulin-producing cells of the pancreas. While research is still underway, the use of GABA for the management of diabetes appears favorable.

Some dietary sources of GABA include tomatoes, broccoli, potatoes, and cabbage. GABA is also available as a dietary supplement.

Glutamate And GABA – Final Thoughts

• Glutamate and GABA are important neurotransmitters in the body. Glutamate controls excitatory impulses while GABA regulates inhibitory impulses.
• Glutamate plays an important role in the gut-brain axis and can be used to improve gastric motility.
• GABA is helpful in maintaining brain functions such as behavior, sleep and cognition.
• GABA has anti-diabetic properties namely – regulating insulin secretion, regenerating insulin-secreting cells of the pancreas, and reducing glucose levels.

References

• Al-Kuraishy HM, Hussian NR, Al-Naimi MS, Al-Gareeb AI, Al-Mamorri F, Al-Buhadily AK. The Potential Role of Pancreatic γ-Aminobutyric Acid (GABA) in Diabetes Mellitus: A Critical Reappraisal. Int J Prev Med. 2021 Feb 24;12:19. doi: 10.4103/ijpvm.IJPVM_278_19.
• Baj A, Moro E, Bistoletti M, Orlandi V, Crema F, Giaroni C. Glutamatergic Signaling Along The Microbiota-Gut-Brain Axis. Int J Mol Sci. 2019 Mar 25;20(6):1482. doi: 10.3390/ijms20061482.
• Liu Y, Weng W, Wang S, Long R, Li H, Li H, Li T, Wu M. Effect of γ-Aminobutyric Acid-Chitosan Nanoparticles on Glucose Homeostasis in Mice. ACS Omega. 2018 Mar 31;3(3):2492-2497. doi: 10.1021/acsomega.7b01988.
• Mittal R, Debs LH, Patel AP, Nguyen D, Patel K, O’Connor G, Grati M, Mittal J, Yan D, Eshraghi AA, Deo SK, Daunert S, Liu XZ. Neurotransmitters: The Critical Modulators Regulating Gut-Brain Axis. J Cell Physiol. 2017 Sep;232(9):2359-2372. doi: 10.1002/jcp.25518.
• Ochoa-de la Paz LD, Gulias-Canizo R, Ruiz-Leyja ED, Sanchez-Castillo H, Parodi J. The Role of GABA Neurotransmitter In The Human Central Nervous System, Physiology, And Pathophysiology. Revista Mexicana de Neurociencia 2-21;22(2)
• Teramoto H, Shimizu T, Yogo H, Nishimiya Y, Hori S, Kosugi T, Nakayama S. Gastric emptying and duodenal motility upon intake of a liquid meal with monosodium glutamate in healthy subjects. Physiol Rep. 2014 Jan 6;2(1):e00187. doi: 10.1002/phy2.187.
• Tsurugizawa T, Torii K. Physiological roles of glutamate signaling in gut and brain function. Biol Pharm Bull. 2010;33(11):1796-9. doi: 10.1248/bpb.33.1796.