What Is Glutamine? Other Names: Acide Glutamique, Levoglutamide, 5-Oxopentanoic Acid

What is Glutamine?

This post was written with Consensus AI Academic Search Engine – please read our Disclaimer at the end of this article. Glutamine is the most abundant free amino acid in the human body, playing a crucial role in various physiological processes. It is traditionally classified as a non-essential amino acid, meaning the body can synthesize it under normal conditions. However, during periods of metabolic stress, such as illness or intense physical activity, the body’s demand for glutamine exceeds its production, making it a “conditionally essential” amino acid . Other names include: Acide Glutamique, Acide Glutamique HCl, Acide L-(+)-2-Aminoglutaramique, Acide L-Glutamique, Acide L-Glutamique HCl, Alanyl-L-Glutamine Dipeptide, Éthyle Ester de Glutamine, Éthyle Ester de Glutamine HCl, GLN, Glutamate, Glutamic Acid, Glutamic Acid HCl, Glutamina, Glutaminate, Glutamine Ethyl Ester, Glutamine Ethyl Ester HCl, Glutamine Methyl Ester, Glutamine Peptides, Levoglutamide, Levoglutamine, L-(+)-2-Aminoglutaramic Acid, L-Alanyl-L-Glutamine, L-Glutamic Acid, L-Glutamic Acid HCl, L-Glutamic Acid Hydrochloride, L-Glutamic Acid 5-Amide, L-Glutamine, N-Acetyl-L-Glutamine, Peptides de Glutamine, Q, (S)-2,5-Diamino-5-oxopentanoic Acid.

Physiological Roles of Glutamine

Metabolic Functions

Glutamine serves as a key metabolic fuel for rapidly proliferating cells, including enterocytes and lymphocytes. It is involved in several metabolic pathways, acting as an oxidative fuel, gluconeogenic precursor, and lipogenic precursor. Additionally, glutamine is essential for the synthesis of nucleic acids, nucleotides, amino sugars, and proteins.

Immune Function

Glutamine is vital for the proper functioning of the immune system. It supports lymphocyte proliferation, cytokine production, macrophage activity, and neutrophil bacterial killing. During catabolic stress, such as critical illness or post-surgery, glutamine supplementation has been shown to reduce infection rates and improve immune responses.

Cellular Integrity and Redox Balance

Glutamine plays a significant role in maintaining cellular integrity and redox balance. It is a precursor for the antioxidant glutathione, which helps in mitigating oxidative stress. Glutamine also regulates apoptosis and cell proliferation, contributing to the overall health of cells .

Clinical Applications of Glutamine

Nutritional Support

Given its critical roles, glutamine is often included in specialized nutritional regimens for critically ill patients. Supplementation can enhance nitrogen balance, preserve skeletal muscle mass, and improve gut barrier function, thereby aiding in recovery and reducing hospital stay .

Sports Nutrition

In the realm of sports nutrition, glutamine is recognized for its potential anti-fatigue properties. It helps in glycogen synthesis and ammonia buffering, although its direct impact on physical performance remains inconclusive.

Cancer Metabolism

Recent studies have highlighted the importance of glutamine in cancer metabolism. Tumor cells often exhibit a high dependency on glutamine for biosynthesis and energy production. Targeting glutamine metabolism is being explored as a therapeutic strategy in cancer treatment.

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Adverse Effects of Glutamine

Alterations in Amino Acid Transport and Metabolism

High glutamine intake can impair the transport and distribution of other amino acids, potentially leading to imbalances in amino acid levels in the body.

Chronic glutamine supplementation may disrupt endogenous glutamine synthesis and increase the production of glutamate and ammonia, which can have toxic effects.

Neurological Effects

Glutamine is metabolized into glutamate and ammonia, both of which can have neurological effects. High levels of these metabolites may lead to neurological damage, particularly in vulnerable populations such as preterm infants.

Immune System Alterations

Glutamine has immunomodulating properties, and its chronic consumption may affect immune function. This includes potential changes in lymphocyte proliferation and cytokine production .

Potential Hepatotoxicity

There is evidence suggesting that high plasma levels of glutamine may be associated with liver damage. A case report documented glutamine-induced hepatotoxicity in an athlete, highlighting the need for caution with high-dose supplementation.

Impact on Cancer

There is a concern that chronic glutamine intake might influence tumor growth, although this requires further investigation to establish a definitive link.

Withdrawal Effects

The sudden withdrawal of glutamine after chronic use may lead to health issues due to the body’s adaptive response to high glutamine levels, potentially resulting in a deficiency.

Lack of Effectiveness in Certain Conditions

In some clinical trials, glutamine supplementation did not show significant benefits in reducing treatment-related toxicities, such as mucositis in cancer patients undergoing chemotherapy or radiation therapy .

General Safety Concerns

While some studies suggest that glutamine is generally safe, there is a lack of comprehensive long-term safety data, particularly for chronic consumption by healthy individuals across different age groups.

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How has Glutamine Improved Patient Outcomes?

Reduction in Infections and Complications

Glutamine supplementation significantly reduces the incidence of postoperative infections and complications in critically ill and surgical patients .

It lowers the rates of nosocomial infections and catheter-related infections in ICU patients .

Improvement in Immune Function

Glutamine enhances humoral and T cell immune function indicators, such as IgA, IgM, IgG, CD4+, and the CD4+/CD8+ ratio, while reducing CD8+ levels.

Reduction in Hospital and ICU Stay

Patients receiving glutamine have shorter hospital and ICU stays, as well as reduced duration of mechanical ventilation .

Mortality Rates

Glutamine supplementation is associated with a reduction in hospital mortality rates, although its effect on ICU mortality is less clear .

Metabolic and Nutritional Benefits

Glutamine helps in maintaining albumin, total protein, and prealbumin levels, which are crucial for recovery and overall health.

It also improves glucose metabolism by reducing insulin resistance.

Economic Benefits

The use of glutamine in enteral feeds for critically ill patients results in significant hospital cost savings.

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Glutamine Mechanisms of Action

Metabolic Functions

Glutamine serves as an oxidative fuel, gluconeogenic precursor, and lipogenic precursor, playing a significant role in cellular metabolism .

It is involved in acid-base balance in the kidney, ureogenesis in the liver, and as an oxidative fuel for the intestine and immune cells.

Gene Expression and Protein Activity

Glutamine regulates the expression of several genes related to metabolism, signal transduction, and cell defense, such as p47phox, p22phox, gp91phox, α-actin, and fibronectin .

It activates proteins like ASK1, c-myc, c-jun, and p70s6k, influencing various cellular pathways.

Cellular Integrity and Function

Glutamine is crucial for maintaining cell integrity by regulating apoptosis, cell proliferation, protein synthesis, and degradation.

It influences the redox potential, respiratory burst, insulin resistance, insulin secretion, and extracellular matrix synthesis.

Lysosomal Function

Glutamine regulates lysosomal pH by producing ammonium, which in turn affects lysosomal degradation and cellular activities.

Enzyme Regulation

Glutamine synthetase (GS) catalyzes the formation of glutamine from glutamate and ammonia, playing a key role in nitrogen metabolism and preventing excitotoxicity in the brain .

GS activity is regulated by feedback inhibition, protein configuration changes, covalent modifications, and transcriptional and post-transcriptional mechanisms .

Glutamine Sensing

In plants, a glutamine-sensing mechanism involving the PII signaling protein regulates the enzyme N-acetyl-l-glutamate kinase (NAGK), which is crucial for arginine and polyamine formation.

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Common Complaints Associated with Glutamine Use

Gastrointestinal Issues

Glutamine supplementation may help reduce chemotherapy-associated mucositis and irinotecan-associated diarrhea, but these benefits suggest that gastrointestinal issues are a common concern in the absence of supplementation.

Neurological Complaints

There is evidence that glutamine can decrease paclitaxel-induced neuropathy, indicating that neuropathy is a significant issue that glutamine aims to address.

Cardiac Complications

Glutamine may reduce the cardiotoxicity associated with anthracycline use, highlighting that cardiac complications are a notable concern during cancer treatment.

Infectious Complications

In surgical patients, glutamine supplementation is associated with a lower rate of infectious complications, suggesting that infections are a common issue in these patients.

Hospital Stay and Mortality

Glutamine supplementation is linked to a shorter hospital stay and potentially lower mortality rates in critically ill patients, indicating that prolonged hospital stays and higher mortality are significant concerns without supplementation.

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