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 acid1 6 8. 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 precursor2. Additionally, glutamine is essential for the synthesis of nucleic acids, nucleotides, amino sugars, and proteins1.
Immune Function
Glutamine is vital for the proper functioning of the immune system. It supports lymphocyte proliferation, cytokine production, macrophage activity, and neutrophil bacterial killing7. During catabolic stress, such as critical illness or post-surgery, glutamine supplementation has been shown to reduce infection rates and improve immune responses10.
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 cells3 9.
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 stay1 8 10.
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 inconclusive5.
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 treatment4.
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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 body1.
Chronic glutamine supplementation may disrupt endogenous glutamine synthesis and increase the production of glutamate and ammonia, which can have toxic effects1.
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 infants2.
Immune System Alterations
Glutamine has immunomodulating properties, and its chronic consumption may affect immune function. This includes potential changes in lymphocyte proliferation and cytokine production1 7.
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 supplementation6.
Impact on Cancer
There is a concern that chronic glutamine intake might influence tumor growth, although this requires further investigation to establish a definitive link1.
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 deficiency1.
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 therapy8 9.
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 groups2.
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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 patients1 2 3 4 5 7 9.
It lowers the rates of nosocomial infections and catheter-related infections in ICU patients5 7.
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+ levels2.
Reduction in Hospital and ICU Stay
Patients receiving glutamine have shorter hospital and ICU stays, as well as reduced duration of mechanical ventilation3 4 6 9.
Mortality Rates
Glutamine supplementation is associated with a reduction in hospital mortality rates, although its effect on ICU mortality is less clear3 5 7.
Metabolic and Nutritional Benefits
Glutamine helps in maintaining albumin, total protein, and prealbumin levels, which are crucial for recovery and overall health4.
It also improves glucose metabolism by reducing insulin resistance1.
Economic Benefits
The use of glutamine in enteral feeds for critically ill patients results in significant hospital cost savings10.
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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 metabolism1 2.
It is involved in acid-base balance in the kidney, ureogenesis in the liver, and as an oxidative fuel for the intestine and immune cells2.
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 fibronectin1 2 4.
It activates proteins like ASK1, c-myc, c-jun, and p70s6k, influencing various cellular pathways2.
Cellular Integrity and Function
Glutamine is crucial for maintaining cell integrity by regulating apoptosis, cell proliferation, protein synthesis, and degradation1.
It influences the redox potential, respiratory burst, insulin resistance, insulin secretion, and extracellular matrix synthesis1.
Lysosomal Function
Glutamine regulates lysosomal pH by producing ammonium, which in turn affects lysosomal degradation and cellular activities3.
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 brain6 7 8.
GS activity is regulated by feedback inhibition, protein configuration changes, covalent modifications, and transcriptional and post-transcriptional mechanisms7 9 10.
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 formation9.
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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 supplementation1.
Neurological Complaints
There is evidence that glutamine can decrease paclitaxel-induced neuropathy, indicating that neuropathy is a significant issue that glutamine aims to address1.
Cardiac Complications
Glutamine may reduce the cardiotoxicity associated with anthracycline use, highlighting that cardiac complications are a notable concern during cancer treatment1.
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 patients2.
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 supplementation2.
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Disclaimer
The content presented in this blog is generated by Consensus, an AI-powered academic search engine, and is based on publicly available scientific literature. While every effort is made to provide accurate, up-to-date, and well-researched information, the content is intended for informational and educational purposes only. It does not constitute medical advice, diagnosis, or treatment. Always consult a qualified healthcare professional before making any decisions regarding medical conditions, treatments, or medications. The AI system’s analysis may not cover all perspectives, emerging research, or individual cases, and it is not a substitute for professional expertise. Neither the blog publisher nor the developers of the AI-powered search engine are responsible for any actions taken based on the information provided in this content. Use of this information is at your own risk. Citations to the original scientific studies are included for reference, but these studies should be reviewed in full and interpreted with the guidance of a healthcare or research professional.
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