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Nutrients Oct 2018Glutamine is the most abundant and versatile amino acid in the body. In health and disease, the rate of glutamine consumption by immune cells is similar or greater than... (Review)
Review
Glutamine is the most abundant and versatile amino acid in the body. In health and disease, the rate of glutamine consumption by immune cells is similar or greater than glucose. For instance, in vitro and in vivo studies have determined that glutamine is an essential nutrient for lymphocyte proliferation and cytokine production, macrophage phagocytic plus secretory activities, and neutrophil bacterial killing. Glutamine release to the circulation and availability is mainly controlled by key metabolic organs, such as the gut, liver, and skeletal muscles. During catabolic/hypercatabolic situations glutamine can become essential for metabolic function, but its availability may be compromised due to the impairment of homeostasis in the inter-tissue metabolism of amino acids. For this reason, glutamine is currently part of clinical nutrition supplementation protocols and/or recommended for immune suppressed individuals. However, in a wide range of catabolic/hypercatabolic situations (e.g., ill/critically ill, post-trauma, sepsis, exhausted athletes), it is currently difficult to determine whether glutamine supplementation (oral/enteral or parenteral) should be recommended based on the amino acid plasma/bloodstream concentration (also known as glutaminemia). Although the beneficial immune-based effects of glutamine supplementation are already established, many questions and evidence for positive in vivo outcomes still remain to be presented. Therefore, this paper provides an integrated review of how glutamine metabolism in key organs is important to cells of the immune system. We also discuss glutamine metabolism and action, and important issues related to the effects of glutamine supplementation in catabolic situations.
Topics: Dietary Supplements; Enteral Nutrition; Glutamine; Humans; Parenteral Nutrition
PubMed: 30360490
DOI: 10.3390/nu10111564 -
Yonsei Medical Journal Nov 2011Dietary supplementation with nutrients enhancing immune function is beneficial in patients with surgical and critical illness. Malnutrition and immune dysfunction are... (Review)
Review
Dietary supplementation with nutrients enhancing immune function is beneficial in patients with surgical and critical illness. Malnutrition and immune dysfunction are common features in hospitalized patients. Specific nutrients with immunological and pharmacological effects, when consumed in amounts above the daily requirement, are referred to as immune-enhancing nutrients or immunonutrients. Supplementation of immunonutrients is important especially for patients with immunodeficiency, virus or overwhelming infections accompanied by a state of malnutrition. Representative immunonutrients are arginine, omega-3 fatty acids, glutamine, nucleotides, beta-carotene, and/or branched-chain amino acids. Glutamine is the most abundant amino acid and performs multiple roles in human body. However, glutamine is depleted from muscle stores during severe metabolic stress including sepsis and major surgery. Therefore it is considered conditionally essential under these conditions. This review discusses the physiological role of glutamine, mode and dose for glutamine administration, as well as improvement of certain disease state after glutamine supplementation. Even though immunonutrition has not been widely assimilated by clinicians other than nutritionists, immunonutrients including glutamine may exert beneficial influence on diverse patient populations.
Topics: Animals; Critical Illness; Glutamine; Humans; Immunity; Inflammation; Malnutrition
PubMed: 22028151
DOI: 10.3349/ymj.2011.52.6.892 -
Physiological Research Mar 2022The aim of the article is to examine side effects of increased dietary intake of amino acids, which are commonly used as a dietary supplement. In addition to toxicity,...
The aim of the article is to examine side effects of increased dietary intake of amino acids, which are commonly used as a dietary supplement. In addition to toxicity, mutagenicity and carcinogenicity, attention is focused on renal and gastrointestinal tract functions, ammonia production, and consequences of a competition with other amino acids for a carrier at the cell membranes and enzymes responsible for their degradation. In alphabetic order are examined arginine, beta-alanine, branched-chain amino acids, carnosine, citrulline, creatine, glutamine, histidine, beta -hydroxy- beta -methylbutyrate, leucine, and tryptophan. In the article is shown that enhanced intake of most amino acid supplements may not be risk-free and can cause a number of detrimental side effects. Further research is necessary to elucidate effects of high doses and long-term consumption of amino acid supplements on immune system, brain function, muscle protein balance, synthesis of toxic metabolites, and tumor growth and examine their suitability under certain circumstances. These include elderly, childhood, pregnancy, nursing a baby, and medical condition, such as diabetes and liver disease. Studies are also needed to examine adaptive response to a long-term intake of any substance and consequences of discontinuation of supplementation.
Topics: Aged; Amino Acids; Arginine; Child; Dietary Supplements; Female; Glutamine; Histidine; Humans; Muscle, Skeletal; Pregnancy
PubMed: 35043647
DOI: 10.33549/physiolres.934790 -
International Journal of Molecular... May 2017Glutamine, the most abundant free amino acid in the human body, is a major substrate utilized by intestinal cells. The roles of glutamine in intestinal physiology and... (Review)
Review
Glutamine, the most abundant free amino acid in the human body, is a major substrate utilized by intestinal cells. The roles of glutamine in intestinal physiology and management of multiple intestinal diseases have been reported. In gut physiology, glutamine promotes enterocyte proliferation, regulates tight junction proteins, suppresses pro-inflammatory signaling pathways, and protects cells against apoptosis and cellular stresses during normal and pathologic conditions. As glutamine stores are depleted during severe metabolic stress including trauma, sepsis, and inflammatory bowel diseases, glutamine supplementation has been examined in patients to improve their clinical outcomes. In this review, we discuss the physiological roles of glutamine for intestinal health and its underlying mechanisms. In addition, we discuss the current evidence for the efficacy of glutamine supplementation in intestinal diseases.
Topics: Animals; Glutamine; Humans; Inflammatory Bowel Diseases; Intestinal Mucosa; Intestines
PubMed: 28498331
DOI: 10.3390/ijms18051051 -
Nutrients Apr 2019Glutamine is a conditionally essential amino acid widely used in sports nutrition, especially because of its immunomodulatory role. Notwithstanding, glutamine plays... (Review)
Review
Glutamine is a conditionally essential amino acid widely used in sports nutrition, especially because of its immunomodulatory role. Notwithstanding, glutamine plays several other biological functions, such as cell proliferation, energy production, glycogenesis, ammonia buffering, maintenance of the acid-base balance, among others. Thus, this amino acid began to be investigated in sports nutrition beyond its effect on the immune system, attributing to glutamine various properties, such as an anti-fatigue role. Considering that the ergogenic potential of this amino acid is still not completely known, this review aimed to address the main properties by which glutamine could delay fatigue, as well as the effects of glutamine supplementation, alone or associated with other nutrients, on fatigue markers and performance in the context of physical exercise. PubMed database was selected to examine the literature, using the keywords combination "glutamine" and "fatigue". Fifty-five studies met the inclusion criteria and were evaluated in this integrative literature review. Most of the studies evaluated observed that glutamine supplementation improved some fatigue markers, such as increased glycogen synthesis and reduced ammonia accumulation, but this intervention did not increase physical performance. Thus, despite improving some fatigue parameters, glutamine supplementation seems to have limited effects on performance.
Topics: Exercise; Fatigue; Glutamine; Humans; Sports Nutritional Sciences
PubMed: 30999561
DOI: 10.3390/nu11040863 -
Journal of Neurochemistry Aug 2006Neurons are metabolically handicapped in the sense that they are not able to perform de novo synthesis of neurotransmitter glutamate and gamma-aminobutyric acid (GABA)... (Review)
Review
Neurons are metabolically handicapped in the sense that they are not able to perform de novo synthesis of neurotransmitter glutamate and gamma-aminobutyric acid (GABA) from glucose. A metabolite shuttle known as the glutamate/GABA-glutamine cycle describes the release of neurotransmitter glutamate or GABA from neurons and subsequent uptake into astrocytes. In return, astrocytes release glutamine to be taken up into neurons for use as neurotransmitter precursor. In this review, the basic properties of the glutamate/GABA-glutamine cycle will be discussed, including aspects of transport and metabolism. Discussions of stoichiometry, the relative role of glutamate vs. GABA and pathological conditions affecting the glutamate/GABA-glutamine cycling are presented. Furthermore, a section is devoted to the accompanying ammonia homeostasis of the glutamate/GABA-glutamine cycle, examining the possible means of intercellular transfer of ammonia produced in neurons (when glutamine is deamidated to glutamate) and utilized in astrocytes (for amidation of glutamate) when the glutamate/GABA-glutamine cycle is operating. A main objective of this review is to endorse the view that the glutamate/GABA-glutamine cycle must be seen as a bi-directional transfer of not only carbon units but also nitrogen units.
Topics: Ammonia; Animals; Biological Transport; Glutamic Acid; Glutamine; Homeostasis; Humans; gamma-Aminobutyric Acid
PubMed: 16787421
DOI: 10.1111/j.1471-4159.2006.03913.x -
Biomolecules Apr 2022In recent years, an increasingly more in depth understanding of tumor metabolism in tumorigenesis, tumor growth, metastasis, and prognosis has been achieved. The broad... (Review)
Review
In recent years, an increasingly more in depth understanding of tumor metabolism in tumorigenesis, tumor growth, metastasis, and prognosis has been achieved. The broad heterogeneity in tumor tissue is the critical factor affecting the outcome of tumor treatment. Metabolic heterogeneity is not only found in tumor cells but also in their surrounding immune and stromal cells; for example, many suppressor cells, such as tumor-associated macrophages (TAMs), myeloid-derived suppressor cells (MDSCs), and tumor-associated T-lymphocytes. Abnormalities in metabolism often lead to short survival or resistance to antitumor therapy, e.g., chemotherapy, radiotherapy, targeted therapy, and immunotherapy. Using the metabolic characteristics of the tumor microenvironment to identify and treat cancer has become a great research hotspot. This review systematically addresses the impacts of metabolism on tumor cells and effector cells and represents recent research advances of metabolic effects on other cells in the tumor microenvironment. Finally, we introduce some applications of metabolic features in clinical oncology.
Topics: Glucose; Glutamine; Humans; Lipid Metabolism; Myeloid-Derived Suppressor Cells; Neoplasms; Tumor Microenvironment
PubMed: 35454171
DOI: 10.3390/biom12040580 -
Cell Communication and Signaling : CCS Jul 2022Metabolic reprogramming and immune escape play a major role in tumorigenesis. Increasing number of studies have shown that reprogramming of glutamine metabolism is a... (Review)
Review
Metabolic reprogramming and immune escape play a major role in tumorigenesis. Increasing number of studies have shown that reprogramming of glutamine metabolism is a putative determinant of the anti-tumor immune response in the tumor microenvironment (TME). Usually, the predatory uptake of glutamine by tumor cells in the TME results in the limited utilization of glutamine by immune cells and affects the anti-tumor immune response. The cell-programmed glutamine partitioning also affects the anti-tumor immune response. However, the reprogramming of glutamine metabolism in tumors modulates immune escape by regulating tumor PD-L1 expression. Likewise, the reprogramming of glutamine metabolism in the immune cells also affects their immune function. Additionally, different types of glutamine metabolism inhibitors extensively regulate the immune cells in the TME while suppressing tumor cell proliferation. Herein, we discuss how metabolic reprogramming of tumor and immune cells regulates anti-tumor immune responses, as well as functional changes in different immune cells in the context of targeting tumor glutamine metabolism, which can better explain the potential of targeting glutamine metabolism in combination with immunotherapy for cancer. Video abstract.
Topics: Glutamine; Humans; Immunity; Immunotherapy; Neoplasms; Tumor Microenvironment
PubMed: 35897036
DOI: 10.1186/s12964-022-00909-0 -
The Journal of Nutrition Oct 2008Some athletes can have high intakes of l-glutamine because of their high energy and protein intakes and also because they consume protein supplements, protein... (Review)
Review
Some athletes can have high intakes of l-glutamine because of their high energy and protein intakes and also because they consume protein supplements, protein hydrolysates, and free amino acids. Prolonged exercise and periods of heavy training are associated with a decrease in the plasma glutamine concentration and this has been suggested to be a potential cause of the exercise-induced immune impairment and increased susceptibility to infection in athletes. However, several recent glutamine feeding intervention studies indicate that although the plasma glutamine concentration can be kept constant during and after prolonged strenuous exercise, the glutamine supplementation does not prevent the postexercise changes in several aspects of immune function. Although glutamine is essential for lymphocyte proliferation, the plasma glutamine concentration does not fall sufficiently low after exercise to compromise the rate of proliferation. Acute intakes of glutamine of approximately 20-30 g seem to be without ill effect in healthy adult humans and no harm was reported in 1 study in which athletes consumed 28 g glutamine every day for 14 d. Doses of up to 0.65 g/kg body mass of glutamine (in solution or as a suspension) have been reported to be tolerated by patients and did not result in abnormal plasma ammonia levels. However, the suggested reasons for taking glutamine supplements (support for immune system, increased glycogen synthesis, anticatabolic effect) have received little support from well-controlled scientific studies in healthy, well-nourished humans.
Topics: Acid-Base Equilibrium; Communicable Disease Control; Dietary Proteins; Dietary Supplements; Energy Metabolism; Exercise; Fatigue; Glutamine; Humans; Immune System; Metabolism; Muscle, Skeletal; Sports
PubMed: 18806122
DOI: 10.1093/jn/138.10.2045S -
Advances in Experimental Medicine and... 2021Metabolism is a fundamental process for all cellular functions. For decades, there has been growing evidence of a relationship between metabolism and malignant cell...
Metabolism is a fundamental process for all cellular functions. For decades, there has been growing evidence of a relationship between metabolism and malignant cell proliferation. Unlike normal differentiated cells, cancer cells have reprogrammed metabolism in order to fulfill their energy requirements. These cells display crucial modifications in many metabolic pathways, such as glycolysis and glutaminolysis, which include the tricarboxylic acid (TCA) cycle, the electron transport chain (ETC), and the pentose phosphate pathway (PPP) [1]. Since the discovery of the Warburg effect, it has been shown that the metabolism of cancer cells plays a critical role in cancer survival and growth. More recent research suggests that the involvement of glutamine in cancer metabolism is more significant than previously thought. Glutamine, a nonessential amino acid with both amine and amide functional groups, is the most abundant amino acid circulating in the bloodstream [2]. This chapter discusses the characteristic features of glutamine metabolism in cancers and the therapeutic options to target glutamine metabolism for cancer treatment.
Topics: Citric Acid Cycle; Energy Metabolism; Glutamine; Glycolysis; Humans; Metabolic Networks and Pathways; Neoplasms
PubMed: 34014532
DOI: 10.1007/978-3-030-65768-0_2