Glutamine is a key component in the metabolism of the immune system, affecting proliferative, phagocytic, and secretory capacities. Its metabolism and utilization by immune cells raise interesting questions regarding the therapeutic manipulation of glutamine levels. In the present article, we will explore the possible therapeutic applications of glutamine to the immune system. In addition, we will discuss how glutamine influences the immune system in several different ways.
L-Glutamine is an essential nutrient for cell proliferation
Although L-glutamine is normally a non-essential amino acid, it may become conditionally essential in inflammatory conditions. It may act as a respiratory fuel and improve the function of immune cells when they are stimulated. Studies have shown that extracellular glutamine concentration can affect lymphocyte proliferation and neutrophil bacterial killing, but more research is needed to understand how it impacts other immune system cells.
The metabolism of L-glutamine is critical for immune system cells during post-injury or infection states. Because immune system cells have similar metabolic characteristics, hypotheses must account for the high utilization of glutamine. For example, lymphocytes retain the capacity to divide rapidly even after being terminally differentiated. Macrophages have high metabolic requirements and secrete cytokines and free radicals. The glutamine mechanism needs to account for diverse secretory products, cell division, and immune function.
It is required for activation and function of immune cells
Glutamine is one of the most abundant and versatile amino acids found in the human body. It is essential for intermediary metabolism, interorgan nitrogen exchange, pH homeostasis, nucleotide synthesis, and numerous biosynthetic pathways. The cellular functions glutamine supports include immune cell activation, differentiation, and cytokine production. Glutamine plays a pivotal role in the immune system.
Glutamine is necessary for NET action by modulating the synthesis of proteins, enzymes, and protective responses to damage. It has antioxidant and cytoprotective effects. Inflammation causes the release of reactive oxygen species, which cause pro-apoptotic stimuli. Glutamate also influences the expression of heat shock proteins. This explains the diverse roles of glutamine in the immune system.
It inhibits tumor growth by altering suppressive myeloid cells
Increasing glutamine levels in cancer cells promotes mTORC1 activation, which supports oncogenic growth. Moreover, glutamine metabolism supports redox homeostasis in cancer cells, and it helps restore oxidized glutathione. As a result, glutamine is a key modulator of cellular metabolism and may hold the key to deciphering cancer metabolism.
The metabolite of glutamine plays a vital role in anabolic growth. It is required for Warburg metabolism, which enables robust tumor growth. JHU083, a glutamine metabolism inhibitor, inhibits the enzyme in the human body. This drug was used to treat 4T1 tumor-bearing mice for 7 days, then switched to a lower dose to kill the mice.
It impinges upon nutrient-sensitive signalling pathways
L-Glutamine, an amino acid that plays a vital role in the regulation of skeletal muscle, is known to affect multiple aspects of the immune system. It impinges upon signalling pathways involved in immune and metabolism, including cytokine release, redox balance, and glutathione. Recent findings suggest that L-Glutamine may be an important factor in regulating the immune system in patients with type 1 diabetes.
Several studies have shown that glutamine enhances the HSP response in both chronic and acute inflammation. In addition, glutamine activates certain intracellular nutrient sensors, including sirtuin 1. Some evidence suggests that glutamine stimulates the transcription of HSF-1 and the heat shock element p53. Further, sirtuin 1 acts on a wide range of substrates, including histones, NFkB, p53, and NFkB.
It affects lymphocyte proliferation
Glutamine plays several roles in the lymphocyte’s metabolism. It is a precursor for amino acid synthesis and a nitrogen donor in the formation of nucleic acids. It also aids in the synthesis of intracellular proteins and contributes to acid-base balance. It has anti-inflammatory and cytotoxic effects. Moreover, it promotes the action of an enzyme in the cytoplasm called NADP+-dependent kinase.
Glutamine is also a crucial nutrient for neutrophils. It improves their bactericidal ability and kills Staphylococcus aureus. The inclusion of glutamine restored neutrophil function to normal. Glutamine also affects the expression of surface activation markers and cytokines. In addition, it protects neutrophils from apoptosis.