L-Glutamine - the Most Abundant Amino Acid

What is L-Glutamine

L-Glutamine is an amide of glutamic acid and it is the most abundant amino acid in the intracellular and extracellular fluid, as well as the bloodstream. It is produced by the action of glutamine synthase and it is required for the production of nitrogen and various cellular functions.  In the bloodstream, L-Glutamine makes up 30 to 35 percent of the amino acid nitrogen.

Glutamine transports nitrogen between cells and/or organs and serves as metabolic fuel—in addition to glucose, or as an alternative—in rapidly proliferating cells. Apart from playing a central role in nitrogen production, glutamine is also crucial for protein and energy metabolism where it acts as a precursor for protein, nucleotide, and nucleic acid synthesis. 

The concentration of glutamine in the blood reflects the short-term balance between exogenous supply, endogenous release, and consumption by organs and cells; while concentrations of glutamine in the muscle tissue represent more than 50% of the body glutamine pool (Stehle & Kuhn, 2015). The plasma concentration of glutamine can be significantly reduced under severe shock, stress and trauma, after rigorous exercise, during fasting and in patients with untreated diabetes mellitus. 

Conditions like this would lead to catabolic stress where intracellular glutamine levels may drop below 50% and plasma concentration below 30%. In this case the body would need to depend on dietary glutamine supplementation.

Glutamate - Glutamine

Deamination of glutamine via glutaminase produces glutamate, a precursor of gamma-amino butyric acid (GABA) known as inhibitory neurotransmitter. Glutamate is the most abundant free amino acid in the brain and is important for cognition, memory and learning. An ongoing scientific research defines glutamate as the major excitatory transmitter in the brain (Zhou & Danbolt, 2014). Like other signalling substances, the signalling effect of glutamate is not dependent on its chemical nature, but on how cells are programmed to respond when exposed to it.

Because the glutamate receptor proteins are expressed on the surface of the cells in such a way that they can only be activated from the outside, we can say that glutamate exerts its neurotransmitter function from the extracellular fluid. Glutamate is taken up into both glial cells and nerve terminals. Within the cells, glutamate is taken up by the astroglial cells and converted to glutamine. Glutamine is released from the glial cells into to extracellular fluid, and being inactive cannot activate glutamate receptors. Nerve terminals take up glutamine and convert glutamine back to glutamate. This process is referred to as the glutamate-glutamine pathway, and is important because it allows glutamate to be inactivated by glial cells and transported back to neurons in an inactive (non-toxic) form.

The Benefits of L-Glutamine

Improves gastrointestinal health

L-glutamine is highly beneficial for any type of digestive issue, such as irritable bowel syndrome (IBS), an inflammatory bowel disease like Crohn’s disease, ulcerative colitis, diverticulosis, diverticulitis, leaky gut or any of the issues associated with leaky gut (like joint pain, rosacea or any type of autoimmune response).  This is because gut mucosa is the major site of glutamine metabolism. In the gut mucosa, glutamine acts as an important substrate where it accounts for about 35% of the production of total carbon dioxide. Glutamine also mediates several other protective influences on the gastrointestinal tract and it is an important dietary component to maintain gut mucosal integrity.  

Because glutamine is the major fuel source for cells in the gut mucosa, it can alleviate leaky gut symptoms. Fujita & Sakurai (1997) have demonstrated decrease in intestinal permeability after glutamine supplementation in patients with leaky gut syndrome.  Another study published by Fujita & Sakurai (1997) found that glutamine can also benefit ulcerative colitis and inflammatory bowel disease.

Glutamine has also been demonstrated to improve symptoms of IBS and diarrhoea by balancing mucus production.  A study done by Huffman & Walgren (2003) in which HIV-infected patients with nelfinavir-associated diarrhoea received glutamine 30 g/day or placebo for 10 days, demonstrated a successful ability of glutamine to reduce symptoms of diarrhoea.

Promotes muscle growth and decreases muscle wasting

After an intense workout, the levels of cellular glutamine can drop by 50 percent and plasma levels by 30 percent. Doing approximately one hour of exercise can not only cause a significant reduction of glutamine levels in the body but also suppress immune function, which could then lead to overtraining syndrome. Hoffman et al. (2010) demonstrated an ability of glutamine to boost the immune system and benefit long distance athletes. This is because glutamine is utilised at a high rate in rapidly dividing immune cells where it promotes many functional activities of the same such as T-cell proliferation, B-cell differentiation, phagocytosis, antigen presentation, cytokine and neutrophil superoxide production (Pithon-Curi et al., 2003).

On the other hand, muscle tissue is a major site of glutamine synthesis where it forms the anabolic precursor for muscle growth. Therefore, dropping of the cellular glutamine levels could lead to muscle-wasting, which is a gateway for the body to use the muscle for energy rather than carbohydrates. Glutamine supplementation can prevent this from happening by allowing the muscles to fight and push a bit further, which in turn can boosts strength and helps in the repair of skeletal muscles. A study done by Bowtell et al. (1999), with aim to determine the efficacy of glutamine in promoting carbohydrate storage and muscle glycogen re-synthesis during recovery from exhaustive exercise, found that glutamine supplementation contributes to faster recovery from intense weight training sessions due to its ability to improve muscle hydration.

Burns fat and improves diabetes

L-glutamine is excellent to burn fat and build lean muscle mass by assisting the body in suppressing insulin levels. This enables the body to use up less muscle mass to maintain blood sugar and insulin sensitivity in the cells. Apart from its ability to supress insulin levels, glutamine also has a positive effect on glucose oxidation. A study done by Comar et al. (2016) suggested an ability of glutamine to diminish oxidative stress and reduce inflammatory processes within the β-cells. Comar et al. (2016) further demonstrated the efficacy of glutamine in increasing the secretion of the glucagon-like peptide-1, when administered with a meal, and ability to reduce postprandial glycaemia in type 2 diabetic patients.

References

• Bowtell, J.L., Gelly, K. et al. (1999). The purpose of this study was to determine the efficacy of glutamine in promoting whole body carbohydrate storage and muscle glycogen re-synthesis during recovery from exhaustive exercise. Journal of Applied Physiology. 86(6), 19-23.

• Comar, J.F., Oliveira, D.S. et al. (2016). The Metabolic Responses to L-Glutamine of Livers from Rats with Diabetes Types 1 and 2. Plos One. 4(16), 3-10.

• Fujita, T., Sakurai, K. (1997). Efficacy of glutamine-enriched enteral nutrition in an experimental model of mucosal ulcerative colitis. British Journal of Surgery. 82(6), 749-751.

• Huffman, F.G., Walgren, M.E. (2003). L-glutamine supplementation improves nelfinavir-associated diarrhoea in HIV-infected individuals. HIV Clinical Trials. 4(5), 324-329.

• Pithon-Curi ,T.C., Schumacher,  R.I. et al. (2003). Glutamine delays spontaneous apoptosis in neutrophils. American Journal Cell Physiology. 284(6), 1355–1361.

• Stehle, P., Kuhn, K.S. (2015). Glutamine: An Obligatory Parenteral Nutrition Substrate in Critical Care Therapy. BioMed Research International. 15(7), 32-35.

• Zhou, Y., Danbolt, N.C. (2014). Glutamate as a neurotransmitter in the healthy brain. Journal of Neural Transmission. 121(8), 799–817.